Abstract
Objectives
Mouthwashes, a cornerstone of oral and dental hygiene, play a pivotal role in combating the formation of dental plaque, a leading cause of periodontal disease and dental caries. This study aimed to review the composition of mouthwashes found on retail shelves in Turkey and evaluate their prevalence and side effects, if any.
Methods
The mouthwashes examined were sourced from the 5 largest chain stores in each district of Istanbul. A comprehensive list of the constituents was meticulously recorded. The research was supported by an extensive compilation of references from scholarly databases such as Google Scholar, PubMed, and ScienceDirect. Through rigorous analysis, the relative proportions of mouthwash ingredients and components were determined.
Results
A total of 45 distinctive variations of mouthwashes, representing 17 prominent brands, were identified. Amongst the 116 ingredients discovered, 70 were evaluated for potential adverse effects and undesirable side effects. The aroma of the mouthwash (n = 45; 100%), as welll as their sodium fluoride (n = 28; 62.22%), sodium saccharin (n = 29; 64.44%), sorbitol (n = 21; 46.6%), and propylene glycol (n = 28; 62.22%) content were the main undesireable features.
Conclusions
The limited array of mouthwashes found on store shelves poses a concern for both oral and public health. Furthermore, the intricate composition of these products, consisting of numerous ingredients with the potential for adverse effects, warrants serious attention. Both clinicians and patients should acknowledge the importance and unwarranted side effects of the compnents of the mouthwashes.
Key words: Adverse effects, Components of mouthwashes, Dental hygiene, Mouthwashes, Oral health
Introduction
Oral health represents a vital component of overall well-being and profoundly impacts one's quality of life, potentially leading to pain, illness, and dental ailments if unattended. Neglected oral health can hinder educational pursuits and productivity, there by extracting an economic cost too. Moreover, good oral health has implications for healthy ageing, encompassing aspects such as nutrition, career prospects, and effective social interactions.1 The primary avenue to optimise oral health is to eliminate dental plaque biofilm, which is the principal cause of the two major dental ailments caries and periodontal disease.2
Although mouthwashes, with their origins traced back to ancient Chinese medicine and possessing a historical lineage as old as human civilisation itself, underwent transformative refinement to assume their modern form by the late 19th century,3 their utilisation remains less prevalent compared with toothpastes. Furthermore, the preferences of mouthwashes in individuals’ oral hygiene practices appear to be influenced by various sociodemographic and behavioural factors.4, 5, 6 Analogous to toothpaste, mouthwashes encompass a repertoire of antibacterial, antimalodour, and antioxidant components, which have demonstrated their efficacy in controlling plaque buildup as well as in preventing periodontal disease and dental caries.7, 8, 9, 10 However, it is noteworthy that a few constituents present in mouthwashes, such as paraben, sodium lauryl sulphate, chlorhexidine (CHX), and ethanol, have been associated with potential side effects including discolouration of tooth-coloured restorations,11 taste disturbances,12 and allergic reactions.13 Notably, claims linking certain types of mouthwash to an increased risk of oral cancer14 have been proposed, although these assertions lack substantial support from epidemiologic evidence.15
Recently, there has been a growing surge in research investigating the constituents of mouthwashes. Whilst studies examining the ingredients of toothpastes have been conducted in Turkey16 and mouthwashes in Poland,17 no previous research has explored the composition of commercially available mouthwashes in the Turkish market. In this context, the present study is an innovative and pioneering approach where the contents of mouthwashes are comprehensively examined and presented for the first time. The primary objective of this study was to investigate the effects of the components of mouthwashes available in the Turkish market including pharmaceutial outlets. Furthermore, we provide a review of the literature on the potential adverse effects or toxic impacts of their major constituents.
Methods
The research was conducted between September 2021 and April 2022. In accordance with the preliminary study prepared by the Competition Authority, the leading supermarket chains dominating the market share nationwide were visited, specifically their largest stores in each region of Istanbul. The focus of the investigation centred on examining the contents of mouthwashes available in the oral care aisles.18 Moreover, by accessing the data from 2 major pharmaceutical warehouses that supply drugs to all pharmacies in Istanbul, a list of mouthwashes sold in pharmacies has been obtained. In the largest stores of the main supermarket chains with the highest market share across various regions of Istanbul and pharmacies, a total of 45 distinct mouthwash variants belonging to 15 different brands were identified and available for purchase. To facilitate comprehensive analysis, all mouthwash labels were meticulously collected and organised within an archive. Each unique ingredient was diligently recorded in alphabetical order using an Excel spreadsheet. Subsequently, extensive literature searches were conducted utilising renowned scholarly search engines such as PubMed, Google Scholar, and ScienceDirect. The primary objective was to investigate the purpose of each unique ingredient present in mouthwash and explore the potential side effects it might engender on human physiology. The findings were then carefully compiled and presented in a tabulated format. Furthermore, the frequency of occurrence for each ingredient across all the mouthwashes included in this study was calculated and expressed as a percentage, as documented in Table 1. All brand and model names of the mouthwashes mentioned in present study, along with their countries of origin, are given in Table 2. Furthermore, ingredients with similar usage purposes and the function performed have been categorised amongst themselves (Table 3).
Table 1.
Ingredients found in common mouthwashes and their properties
| Ingredient | Frequency of occurrence, No. (%) | Functionality | Likely adverse effect/s |
|---|---|---|---|
| Abies sibirica oil | 1 (2.22%) | Antifungal activity117 | Minimal functional and histologic effect in mice117 |
| Acid Orange 7 (CI 15510) | 1 (2.22%) | Dye | Discolouration, gastrointestinal problems |
| Alcohol (ethylalcohol) | 3 (6.67%) | Solvent46 | May lead to burning in mouth50 |
| Allantoin | 3 (6.67%) | Influences the cell response positively, promotes gum and oral mucosa118 | Not known |
| Allura Red AC (CI 16035) | 4 (8.88%) | Azo dye (colourant)110 | Asthma, headache, allergic irritation119,120 |
| Aloe barbadensis leaf juice (Aloe vera) | 1 (2.22%) | Antiplaque and antibacterial121 | No side effect122 |
| Aroma | 45 (100%) | Flavouring agent; essence17; beneficial for thirst, halitosis, and sore throat123 | Not known |
| Ascorbic acid | 1 (2.22%) | Antioxidant and antimicrobial124,125 | Excessive accumulation may increase level of lipid peroxidation,126 skin irritation127 |
| Benzyl alcohol | 6 (13.33%) | Essence, preservative,17 dental plaque inhibition128 | It is comparatively safer than ethyl alcohol52,53 |
| Benzoic acid | 8 (17.77%) | Cosmetic preservative17 | Low general toxicity and rarely irritates skin53 |
| BHT (butylated hydroxytoluene) | 1 (2.22%) | Synthetic antioxidant73 | No evidence of skin irritation or contact allergen,73 increased hepatocyte apoptosis and elevated TGF-ß1 because of repeated dose73 |
| Boric acid | 1 (2.22%) | Antibacterial, antifungal, antiviral,129 postoperative painkiller, reduces swelling130 | No adverse effect according to a-double blind randomised study130 |
| Brilliant Blue FCF (CI 42090) | 8 (17.77%) | Colourant131 | Low toxic effect,132 may adsorb synthesised hydroxyapetite nanoparticles?*133 |
| Caprylyl glycol | 1 (2.22%) | Antimicrobial activity,134 preservative booster and enhancer135 | A favourable profile for skin sensitivites135 |
| Calcium glycerophosphate | 1 (2.22%) | Enhancer of remineralisation properties136 | Safe137 |
| Cellulose gum | 1 (2.22%) | Thickener, gelling agent, flavour and taste138 | Anaphylactic reaction139 |
| Cetylpyridinium chloride | 19 (42.22%) | Reducing plaque accumulation and inflamation140 | According to older studies: staining, ulceration and burning mouth,141 low toxicity142 |
| Chlorhexidine digluconate | 7 (17.77%) | Antimicrobial,143 antiviral?†41 | Hypersensitivity reaction,44 may induce dental caries indirectly and cardiovascular problems40 |
| Cinnamal/cinnamon | 7 (15.55%) | Inhibiting hyphal growth of C albicans,65 fragrance17 | Increases the levels of cinnamaldehyde in breath144 |
| Cistus species resin extract | 1 (2.22%) | Antimicrobial,62 antiviral63 | None found |
| Citrus aurantium amara fruit extract | 3 (6.66%) | Conditioner, stimulant145 | Increasing blood pressure and tachycardia145 |
| Citric acid | 12 (26.66%) | Buffering, pH regulator17 | Bad feel in mouth,146 may induce oral adverse effect such as dentin hypersensitivity or demineralisation147 |
| Cyclodextrin | 1 (2.2%) | Enables the reduction of viral load,148 utilising drug delivery system and solubilising149 | Especially certain types are well tolerated by the human body with no adverse effect150 |
| Dipotassium oxalate | 1 (2.22%) | Treat dentin hypersensitivity151 | None found |
| Disodium EDTA | 1 (2.22%) | Antioxidant152 | Fertility-related, developmental toxicity153 |
| Disodium phosphate | 3 (6.66%) | Lower whitening154 | May cause phosphate toxicity155 |
| Ethylparaben | 1 (2.22%) | Preserving156 | Acts like estrogen, may lead to cancer,71 endocrin-disruptor,72 accumulates in urine156 |
| Eucalyptol | 7 (15.55%) | Antibacterial157 | May induce maternal and foetal toxicity55 |
| Eugenol | 3 (6.66%) | Analgesic, antimicrobial, flavoring158 | Contact dermatitis§159 |
| Fast Green FCF (CI 42053) | 6 (13.33%) | Synthetic dye160 | Inhibiting synaptic activity161 |
| Fruit/seed oil | 1 (2.22%) | Antimicrobial162 | None found |
| Gellan gum | 1 (2.22%) | Gaining functional properties, using a replacement for gelatin | Nontoxic163 |
| Glycerin | 31 (68.88%) | Humectant164 | Nephrotoxic and hepatotoxic165 |
| Hydrogen peroxide | 1 (2.22%) | Whitening and antiplaque166 | None found167 |
| Hydroxyapatite | 2 (4.44%) | Remineralisation168 | No adverse effect169 |
| Hydroxyethylcellulose | 1 (2.22%) | Binding, rheology regulator164,170 | Minimal health risk171 |
| Illicium verum (star anise) | 1 (2.22%) | Aroma, bacterial reduction172 | Not known |
| Lactic acid | 3 (6.66%) | Preservative173 | Microplastically threat174 |
| Laminaria saccharina extract | 1 (2.22%) | Antibacterial and antioxidant175 | Not known |
| Linalool | 1 (2.22%) | Solvent, aromatic agent | |
| Magnesium chloride | 1 (2.22%) | Enhancer of remineralisation properties136 | None found |
| Mentha arvensis herb oil | 3 (6.66%) | Antibacterial, antioxidant176 | None found |
| Mentha piperita | 2(4.44%) | Therapeutic,177 menthol-like activity17 | Intermediate level of serious adverse effect178 |
| Menthol | 14 (31.11%) | Various therapeutic and medicinal properties176 | None found |
| Menthone glycerin acetal | 1 (2.22%) | Synthetic menthol | None found |
| Methyl salicylate | 6 (13.33%) | Solvent51 | Chronic toxic effects,45 cardiac asystole51 |
| Methylparaben | 7 (15.55%) | Antimicrobial agent for preserving156 | Acts like estrogen, may lead to cancer,71 endocrine disruptor,72 accumulates in urine156 |
| Neohesperidin dihydrochalcone | 2 (4.44%) | Sweeteners179 | No adverse effect180 |
| O-cymen-5-ol | 1 (2.22%) | Antimicrobial,75 preservative,17 inhibiting enamel demineralisation,76 fragrance ingredient | None found181‡ |
| Panthenol | 2 (4.44%) | Pro-vitamin B5, gum care182 | Safe within limits183 |
| Patent Blue V (CI 42051) | 13 (28.88%) | Dye | Discolouration, gastrointestinal problems |
| PEG-4 hydrogenated castor oil | 1 (2.22%) | Emulsifier, enhancer of penetration184 | No study¶ |
| PEG-40 hydrogenated castor oil | 10 (22.22%) | Surfactant185 | Moderate cytotoxic effects86 |
| PEG-60 hydrogenated castor oil | 3 (6.66%) | Surfactant185 | Moderate cytotoxic effects86 |
| Pentasodium triphosphate | 1 (2.22%) | Making contribution abrasive and removing calculus186 | Irritates eyes and skin187 |
| Peppermint essential oil | 1 (2.22%) | Flavouring, antibacterial, antioxidant188 | Dermatitis, ache, indigestion, tremours188 |
| Phenoxyethanol | 3 (6.66%) | Antiplaque,189 solubilising,190 preservative191 | Well tolerated,191 some adverse effect on skin192 |
| Polysorbate 20 | 5 (11.11%) | Flavouring and solubilising agent193 | Leads to toxicity by increasing permeability of human intestinal epithelial cells90 |
| Polyepsilon lysine | 3 (6.66%) | Antibacterial preservative, emulsifier | Not known |
| Poloxamer 407 | 20 (44.44%) | Inhibiting adhesion of microbiological,31 increasing solubility of active agent and drug delivery91 | May lead to acute and subchronic toxicity91 |
| Poloxamer 338 | 1 (2.22%) | Inhibiting adhesion of microbiological,31 increasing solubility of active agent and drug delivery91 | May lead to acute and subchronic toxicity91 |
| Potassium acesulfame |
5 (11.11%) | Sweeteners194 | May damage liver and nervous system195 |
| Potassium nitrate | 3 (6.66%) | Decreasing dentin hypersensitivty196 | None found |
| Potassium phosphate | 1 (2.22%) | Buffering197 | None found |
| Potassium sorbate | 9 (20%) | Preservation agent198 | Hypersensitivity and asthma66 |
| Propolis | 1 (2.22%) | Antimicrobial, antioxidant, anti-inflammatory199,200 | Localised or systemic contact dermatitis201 |
| Propylene glycol | 28 (62.22%) | Humectant170 | May induce ocular and respiratory irritation as well as skin and organ toxicity71 |
| Propylparaben | 5 (11.11%) | Antimicrobial agent for preserving156 | Acts like estrogen, may induce cancer,71 endocrine disruptor,72 accumulates in urine156 |
| PVM/MA copolymer | 2 (4.44%) | Contributes to the formation of an arginine -rich layer on dentine, thereby mitigating dentine hypersensitivity97 | None found100 |
| PVP | 2 (4.44%) | Remover of external stains, prevents their re-formation202,203 | The proportion of it in toothpaste should be minimised as much as possible204 |
| Olaflur | 1 (2.22%) | Prevents dental caries17 | None found |
| Quercus robur bark extract | 1 (2.22%) | Effective periodontitis treatment and antioxidant,36 antibacterial205 | Not known |
| Quinoline Yellow WS (CI 47005) | 4 (8.88%) | Colouring agent206 | May be carcinogenic and induce tumour proliferation114 |
| Red 33 (CI 17200) | 5 (11.11%) | Colouring agent207 | Not known |
| Stannous fluoride | 1 (2.22%) | Anticaries and biofilm reduction208 | Staining209 |
| Sodium chloride | 2 (4.44%) | Inhibition of bacterial biofilm210 | Osteoporosis and renal stones211 |
| Sodium citrate | 3 (6.66%) | Decreases dentinal hypersensitivity212 | Not known |
| Sodium fluoride | 28 (62.22%) | Anticaries activity32 | Excessive intake results in skeletal and dental issues33 |
| Sodium gluconate | 3 (6.66%) | Chelator164 | Not known |
| Sodium hyaluronate | 1 (2.22%) | Antiplaque,213 cosmetic filler214 | Safe║215 |
| Sodium hydroxide | 7 (15.55%) | Regulator of pH216 | Negative effect on esophageal cells217 |
| Sodium lactate | 1 (2.22%) | Anti-erosive218 | Not known |
| Sodium metabisulfite | 1 (2.22%) | Preservative and antioxidant219 | Allergic contact dermatitis219,220 |
| Sodium methyl cocoyl taurate | 2 (4.44%) | Surfactant221 | Less soft tissue lesions observed in contrast to oral product care containing Sodium lauryl sulfate222 |
| Sodium monofluorophosphate | 2 (4.44%) | Anticaries223 | Excessive intake may lead to dental and skeletal fluorosis224 |
| Sodium phosphate | 3 (6.66%) | Active agent, remineralisation,225 whitening154 | May induce phosphate toxicity82 |
| Sodium propionate | 1 (2.22%) | Therapeutic agent226 | Neurologic damage, hyperglycaemia227 |
| Sodium benzoate | 19 (42.22%) | Protective agent228 | Noticed as a safer preservative71 but had a cytotoxic effect on human gingival fibroblast229 |
| Oxygene (sodium chlorite) | 3 (6.66%) | Biofilm inhibition210 | Not known |
| Sodium lauryl sulphate | 8 (17.77%) | Surfactant, contributing to thickening and foaming230 | The irritant agent induces nuclear morphologic changes155 in oral epithelial cells in various body parts80 |
| Sodium saccharin | 29 (64.44%) | 300 times sweeter than sucrose231,232 | Skin allergy, cardiac, and gastrointestinal problems; induces cancer232; has carcinogenic effects233 |
| Sorbitol | 21 (46.66%) | Sweetener,57 humectant164 | Not known |
| Sunset Yellow FCF (CI 15985) | 1 (2.22%) | Dye234 | Excessive consumption may induce multiple symptoms in childhood,235 may lead to lesions and cancer,236 genotoxic potential on rats237 |
| Tartrazine (CI 19140) | 7 (15.75%) | Dye238 | Induces urticaria and asthma symptoms111 |
| Tetrapotassium pyrophosphate | 3 (6.66%) | Abrasivity and antitartar186,239 | Oral problems, mucosal gingivitis, contact stomatitis239 |
| Tetrasodium pyrophosphate | 2 (4.44%) | Inhibiting of tartar accumulation240 | Irritates eyes and skin241 |
| Thymol | 7 (15.75%) | Antifungal effect, inhibiting the plaque formation and gingivitis,42 bacterial eradication242 | Chronic toxic effects45 |
| Vitamin E | 1 (2.22%) | Antioxidant,243 anti-erosive244 | No information regarding mouthwash |
| VP/VA copolymer | 4 (8.88%) | Lubricant245 | There is a risk assesment246 |
| Xanthan gum | 1 (2.22%) | Stabiliser, thickener agent170 | May lead to flulike syndrome247 |
| Xylitol | 18 (40%) | Anticaries efficacy indirectly248 | Exceeding a certain dose may lead to gastrointestinal problems249 |
| Zeolit | 1 (2.22%) | Hydrated aluminum silicate in crystal structure250 | Safe251 |
| Zinc acetate | 2 (4.44%) | Antigingivitis, remover of dental plaque, antihalitosis252 | Above a certain dosage, its zinc content leads to a toxic effect253 |
| Zinc chloride | 4 (8.88%) | Controlling of oral malodour,254 treatment of oral mucositis102 | Above a certain dosage, its zinc content leads to a toxic effect253 |
| Zinc citrate | 3 (6.66%) | Controlling of oral malodour255; reduces viral density in saliva of patients infected with SARS-CoV-2256; inhibiting calculus formation257 | Above a certain dosage, its zinc content leads to a toxic effect253 |
| Zinc lactate | 3 (6.66%) | Antihalitosis,258 antigingivitis efficient with cetylpyridinium chloride259 | Above a certain dosage, its zinc content leads to a toxic effect253 |
According to Wang et al,133 synthesised hydroxyapatites contribute biologically to the purification of brilliant blue–contaminated water. However, the association between this substance and Hydroxyapatite in dental and composite restorations is uncertain and subject to further investigation.
It has been stated that the risk of bias, especially in clinical studies, is not fully determined and may be close to a high level. No efficacy was found in some in vitro studies.
It is safe to use up to 0.5% in the field of cosmetics, but it has been stated that the studies are not sufficient.
It has been indicated that there is insufficient evidence.
Whilst some types of PEG (PEG/PPG-17/6, PEG-40, PEG-60) may have low-level potential toxic effects, the overall use of PEG products in cosmetics and personal care items is generally considered safe. Specific studies are required to further assess their safety.184
The studies that claim it is safe are not related to mouthwash. Additional research is needed.
Table 2.
Names and origins of all mouthwashes included in present study.
| Brand | Models | Origin |
|---|---|---|
| Colgate | Gum | New York City, United States |
| Optic White | ||
| Plax Complete Care | ||
| Plax Çay ve Limon (Plax Tea and Lemon) | ||
| Plax Nane Ferahlığı (Minty Freshness) | ||
| Plax Taze Nane (Fresh Mint) | ||
| Plax White + Charcoal | ||
| Total 12 | ||
| Üçlü Etki (Triple Effect) | ||
| Curaprox | Perio Plus Forte | Zurich, Switzerland |
| Perio Plus Regenerate | ||
| Perio Plus Balance | ||
| Denta | Nane Ferahlığı (Minty Freshness) | Türkiye |
| DentaSave | Ağız Kokusu (Halitosis) | Drogsan İlaçları, Istanbul, Türkiye |
| Klorhex Diş Eti Bakımı (Klorhex Gum Care) | ||
| Tam Koruma (Full Protection) | ||
| Denthor | Zeolit Çinko İçerikli Ağız Kokusu Giderici (Zeolite Zinc Halitosis Remover) | EcoPharma, Istanbul, Türkiye |
| Eludril | Classic Mouthwash | Paris, France |
| Listerine | Advanced White Hafif Tat (Mild Test) | Lambertville, New Jersey, United States |
| Cool Mint Hafif Tat (Mild Test) | ||
| Cool Mint | ||
| Diş ve Diş Eti Koruması Hafif Tat Ferah Nane (Teeth and Gum Care Mild Test Refreshing Mint) | ||
| Fresh Burst | ||
| Geliştirilmiş Koruma Nane Ferahlığı (Enhanced Protection Minty Freshness) | ||
| Stay White | ||
| Total Care | ||
| Oderol | Ağız Kokusu Önleyici (Halitosis Preventer) | Türkiye |
| Oral-B | Fresh Mint Gum and Enamel Care | Protector Gamble, Ohio, United States |
| Oxyfresh | Cavity Protection | Coeur d'Alene, Idaho, United States |
| Fresh Breath Nane Limon (Mint and Lemon) | ||
| Pro Formula | ||
| Marvis | Ağız Gargarası Spearmint (Mouthwash Spearmint) | Italy |
| Ağız Gargarası Anise Mint (Mouthwash Anise Mint) | ||
| Ağız Gargarası Cinnamon Mint (Mouthwash Cinnamon Mint) | ||
| Meridol | Ağız Bakım Suyu (Mouthwash) | Türkiye |
| Paradontax | Ekstra Ferah (Extra Fresh) | GlaxoSmithKline, England |
| PerioAid | Active Control | Dentaid, Spain |
| Intense Care | ||
| R.O.C.S. | Black Edition | Russia |
| Sensodyne | Cool Mint | GlaxoSmithKline, England |
| Promine | ||
| VITIS | Anticaries | Spain |
| Sensitive | ||
| Orthodontic | ||
| Gingival |
The model name provided in parentheses is the English equivalent of the Turkish names.
Table 3.
Categorisation of ingredients based on their intended usage.
| Categorisation of ingredients | Amongst mouthwashes |
Amongst categorised groups | |
|---|---|---|---|
| Ingredient | No. (%) | (%) | |
| Alcohol (solvent) | Alcohol (ethylalcohol) | 3 (6.67%) | (18.75%) |
| Benzyl alcohol | 6 (13.33%) | (37.5%) | |
| Linalool | 1 (2.22%) | (6.25%) | |
| Methyl salicylate | 6 (13.33%) | (37.5%) | |
| Anticaries | Olaflur | 1 (2.22%) | (2%) |
| Stannous fluoride | 1 (2.22%) | (2%) | |
| Sodium fluoride | 28 (62.22%) | (56%) | |
| Sodium monofluorophosphate | 2 (4.44%) | (4%) | |
| Xylitol | 18 (40%) | (36%) | |
| Anti-erosive | Sodium lactate | 1 (2.22%) | (100%) |
| Antimicrobial | Boric acid | 1 (2.22%) | (100%) |
| Antioxidant | Ascorbic acid | 1 (2.22%) | (33.3%) |
| BHT (butylated hydroxytoluene) | 1 (2.22%) | (33.3%) | |
| Disodium EDTA | 1 (2.22%) | (33.3%) | |
| Antitartar/antiplaque | Pentasodium triphosphate | 1 (2.22%) | (8.33%) |
| Sodium chloride | 2 (4.44%) | (16.66%) | |
| Sodium hyaluronate | 1 (2.22%) | (8.33%) | |
| Oxygene (sodium chlorite) | 3 (6.66%) | (25%) | |
| Tetrapotassium pyrophosphate | 3 (6.66%) | (25%) | |
| Tetrasodium pyrophosphate | 2 (4.44%) | (16.66%) | |
| Buffering | Citric acid | 12 (26.66%) | (60%) |
| Potassium phosphate | 1 (2.22%) | (5%) | |
| Sodium hydroxide | 7 (15.55%) | (35%) | |
| Chlorhexidine | Digluconate | 8 (17.77%) | (100%) |
| Colourants (dye) | Acid Orange 7 (CI 15510) | 1 (2.22%) | (2.04%) |
| Allura Red AC (CI 16035) | 4 (8.88%) | (8.16%) | |
| Brilliant Blue FCF (CI 42090) | 8 (17.77%) | (16.32%) | |
| Fast Green FCF (CI 42053) | 6 (13.33%) | (12.24%) | |
| Patent Blue V (CI 42051) | 13 (28.88%) | (26.53%) | |
| Quinoline Yellow WS (CI 47005) | 4 (8.88%) | (8.16%) | |
| Red 33 (CI 17200) | 5 (11.11%) | (10.20%) | |
| Sunset Yellow FCF (CI 15985) | 1 (2.22%) | (2.04%) | |
| Tartrazine (CI 19140) | 7 (15.75%) | (14.28%) | |
| Essential oils | Abies sibrica oil | 1 (2.22%) | (2.7%) |
| Eucalyptol | 7 (15.55%) | (18.91%) | |
| Eugenol | 3 (6.66%) | (8.1%) | |
| Fruit/seed oil | 1 (2.22%) | (2.7%) | |
| Mentha arvensis herb oil | 3 (6.66%) | (8.1%) | |
| Menthol | 14 (31.11%) | (37.83%) | |
| Peppermint essential oil | 1 (2.22%) | (2.7%) | |
| Thymol | 7 (15.75%) | (18.91%) | |
| Dentin hypersensitivity treatment | Dipotassium oxalate | 1 (2.22%) | (14.28%) |
| Potassium nitrate | 3 (6.66%) | (42.85%) | |
| Sodium citrate | 3 (6.66%) | (42.85%) | |
| Gelling and functional agent | Cellulose gum | 1 (2.22%) | (25%) |
| Gellan gum | 1 (2.22%) | (25%) | |
| Hydroxyethylcellulose | 1 (2.22%) | (25%) | |
| Xanthan gum | 1 (2.22%) | (25%) | |
| Humectant | Glycerin | 31 (68.88%) | (50%) |
| Propylene glycol | 28 (62.22%) | (45.16%) | |
| Sodium gluconate | 3 (6.66%) | (4.83%) | |
| Herbal | Aloe barbadensis leaf juice (aloe vera) | 1 (2.22%) | (5.88%) |
| Cinnamal/cinnamon | 7 (15.55%) | (41.17%) | |
| Cistus species resin extract | 1 (2.22%) | (5.88%) | |
| Citrus aurantium amara furit extract | 3 (6.66%) | (17.64%) | |
| Illicium verum (star anise) | 1 (2.22%) | (5.88%) | |
| Laminaria saccharina extract | 1 (2.22%) | (5.88%) | |
| Mentha piperita | 2 (4.44%) | (11.76%) | |
| Quercus robur bark extract | 1 (2.22%) | (5.88%) | |
| Preservatives | Benzoic acid | 8 (17.77%) | (14.03%) |
| Caprylyl glycol | 1 (2.22%) | (1.75%) | |
| Ethylparaben | 1 (2.22%) | (1.75%) | |
| Lactic acid | 3 (6.66%) | (5.26%) (12.28%) |
|
| Methylparaben | 7 (15.55%) | ||
| Phenoxyethanol | 3 (6.66%) | (5.26%) | |
| Potassium sorbate | 9 (20%) | (15.78%) | |
| Propylparaben | 5 (11.11%) | (8.77%) | |
| Sodium metabisulfite | 1 (2.22%) | (1.75%) | |
| Sodium benzoate | 19 (42.22%) | (33.33%) | |
| Remineralisation | Hydroxyapatite | 2 (4.44%) | (33.33%) |
| Magnesium chloride | 1 (2.22%) | (16.66%) | |
| Sodium phosphate | 3 (6.66%) | (50%) | |
| Surfactants | PEG-4 hydrogenated castor oil | 1 (2.22%) | (1.88%) |
| PEG-40 hydrogenated castor oil | 10 (22.22%) | (18.86%) | |
| PEG-60 hydrogenated castor oil | 3 (6.66%) | (5.66%) | |
| Polysorbate 20 | 5 (11.11%) | (9.43%) | |
| Polyepsilon-lysine | 3 (6.66%) | (5.66%) | |
| Poloxamer 407 | 20 (44.44%) | (37.73%) | |
| Poloxamer 338 | 1 (2.22%) | (1.88%) | |
| Sodium methyl cocoyl taurate | 2 (4.44%) | (3.77%) | |
| Sodium lauryl sulphate | 8 (17.77%) | (15.09%) | |
| Sweeteners | Neohesperidin dihydrochalcone | 2 (4.44%) | (3.5%) |
| Potassium acesulfame | 5 (11.11%) | (8.77%) | |
| Sodium saccharin | 29 (64.44%) | (50.87%) | |
| Sorbitol | 21 (46.66%) | (36.84%) | |
| Specific ingredients | Allantoin | 3 (6.67%) | (6.52%) |
| Calcium glycerophosphate | 1 (2.22%) | (2.17%) | |
| Cetylpyridinium chloride | 19 (42.22%) | (41.3%) | |
| Cyclodextrin | 1 (2.2%) | (2.17%) | |
| Menthone glycerin acetal | 1 (2.22%) | (2.17%) | |
| O-cymen-5-ol | 1 (2.22%) | (2.17%) | |
| Panthenol | 2 (4.44%) | (4.34%) | |
| Propolis | 1 (2.22%) | (2.17%) | |
| PVM/MA copolymer | 2 (4.44%) | (4.34%) | |
| PVP | 2 (4.44%) | (4.34%) | |
| Vitamin E | 1 (2.22%) | (2.17%) | |
| VP/VA copolymer | 4 (8.88%) | (8.69%) | |
| Zeolit | 1 (2.22%) | (2.17%) | |
| Whitening | Disodium phosphate | 3 (6.66%) | (6.52%) |
| Hydrogen peroxide | 1 (2.22%) | (2.17%) | |
| Sodium phosphate | 3 (6.66%) | (6.52%) | |
| Zinc content | Zinc acetate | 2 (4.44%) | (16.66%) |
| Zinc chloride | 4 (8.88%) | (33.33%) | |
| Zinc citrate | 3 (6.66%) | (25%) | |
| Zinc lactate | 3 (6.66%) | (25%) | |
Results
A total of 45 diverse models from 17 distinct brands of mouthwashes were encompassed in this study (n = 45). Amongst the mouthwash brands examined, the following were ranked: Colgate, Curaprox, Denta, DentaSave, Denthor, Eludril, Listerine, Oderol, Oral-B, Oxyfresh, Marvis, Meridol Paradontax, PerioAid, R.O.C.S., Sensodyne, and VITIS. In the entirety of the samples analysed, a comprehensive tally of 116 unique ingredients was identified. The relative frequencies of 106 unique ingredients, derived from dental, medical, or pharmaceutical studies accessed through PubMed, ScienceDirect, and Google Scholar search engines, were calculated as percentages within the domain of that dental product care. Notably, aroma (n = 45; 100%), sodium fluoride (n = 28; 62.22%), sodium saccharin (n = 29; 64.44%), sorbitol (n = 21; 46.66%), propylene glycol (n = 28; 62.2%), poloxamer 338 and 407 (n = 21; 46.66%), glycerin (n = 31; 68.88%), and menthol (n = 14; 31.11%) emerged as some of the most frequently encountered constituents. It was determined that sodium fluoride was present in the range of 217 to 500 ppm in 23 out of 45 different mouthwashes. Additionally, mouthwashes containing sodium fluoride at much lower percentages were also identified (n = 1; 0.05%, n = 3; 0.08%), with a total count of 28. Unfortunately, the specific concentration of sodium fluoride in a single gargle could not be ascertained. It was reported that a total of 21 mouthwashes were found to contain sodium fluoride as the active ingredient. Amongst the 45 mouthwashes examined, it was determined that 1 mouthwash contained dipotassium oxalate as its active ingredient, whilst another mouthwash contained potassium nitrate as its active ingredient. In addition, active ingredients, namely oxygene (n = 3), chlorhexidine digluconate (CHX) (n = 5), and zeolite (n = 1) were also included. Chlorhexidine was present in only 7 out of all mouthwashes, within the range of 0.025% to 0.2%. However, 8 mouthwashes did not specify the active ingredient on its label. Based on the current literature, it has been determined that the 70 distinct ingredients found in this mouthwash have the potential to elicit adverse effects and may pose a threat to human health. Furthermore, it has been reported that certain agents commonly employed in mouthwashes, such as sodium fluoride and sodium saccharin, exert adverse effects on the human body (Table 1).
Discussion
The effectiveness of mouthwashes used for preventive or therapeutic purposes is not solely dependent on the presence or proportion of the active ingredient; it is also associated with various factors such as the duration of usage, the individual's overall health condition, and their awareness of oral hygiene.17,19 To comprehensively address the constantly updated and newly introduced constituents of mouthwashes in the market, to scrutinise their functions, and to identify potential side effects, such a study has not been previously conducted in our country and this research is recorded as the pioneering work in this field.
Mouthwashes play a chemical role in the process of removing dental plaque, but it is essential to recognise that they cannot replace fundamental mechanical cleaning methods on their own.20 When used individually, mouthwashes primarily target the outer layer of the microbiota and may not reach the subgingival area in the absence of tissue pathology. The most effective approach to plaque removal necessitates the combined use of mechanical and chemical cleaning techniques. Mechanical cleaning reduces the plaque mass, leaving behind a residual irregular and disordered plaque that can be effectively eliminated using chemical methods. The impact of mouthwash usage following brushing is comparable to rinsing and serves as a complement to brushing.8 Additionally, mouthwashes contribute to the prevention of dental plaque formation by reducing the microbial count.21 Toothbrushes and toothpastes are paramount in overall oral hygiene practices and are widely preferred in both developed and developing countries.22, 23, 24, 25 In Turkey, toothbrushes and toothpastes are highly popular oral care instruments,19,26 and it has been revealed that toothpastes may contain potentially harmful substances.16 Although mouthwashes are used less frequently than toothpastes, they hold a significant position as one of the most favoured dental and oral care products in Turkey, with an estimated utilisation rate of 30%.5 Given this context, understanding the composition of both toothpaste and mouthwash is crucial. Thus, the aim of this study was to comprehensively investigate the potential adverse effects of mouthwashes ingredients on oral and other bodily tissues.
Fluoride ions rapidly penetrate the enamel and interact with hydroxyapatite in the tooth structure, forming fluoroapatite. As a consequence, fluoroapatite exhibits a more resistant structure against acids compared to hydroxyapatite. Whilst the pH value in the oral environment exceeds the critical threshold, hydroxyapatite normally undergoes dissolution more easily, whereas fluoroapatite is less affected by pH changes.27 Additionally, fluoride ions also directly prevent tooth decay by inhibiting enzymes essential for the survival of microorganisms, such as enolase and proton-extruding ATPases.28 Amongst the mouthwashes included in our study, sodium fluoride, sodium monofluorophosphate, and stannous fluoride were found. The majority of mouthwashes (n = 28; 62.22%) contain sodium fluoride as the active ingredient. However, the concentration of sodium fluoride varies amongst different mouthwash brands. Most mouthwashes have a sodium fluoride concentration of 225 ppm or higher, whilst a few mouthwashes contain less than 225 ppm (n = 9). The exact proportion of sodium fluoride in a single mouthwash could not be determined. A study conducted in Sweden revealed that despite living in a developed country, only one participant was aware of the ppm value of fluoride in their toothpaste, with half of the participants using fluoride-containing toothpaste.22 Furthermore, in the US, it has been found that although there are more than 120 million mouthwash users, only 7% of the mouthwashes contain fluoride.29 This raises questions about societal awareness regarding the presence and potential beneficial or harmful effects of fluoride in oral care products, highlighting the need for further research and discussion on fluoride awareness. Fluoridated mouthwashes have a longer fluoride retention in the oral cavity compared with fluoridated toothpastes, owing to their mechanism of action. Rinsing the mouth with running water after brushing can reduce fluoride retention. Therefore, it is recommended to use fluoride-containing mouthwash after brushing with fluoride-containing toothpaste to enhance its effectiveness.29,30 Whilst other substances such as amin fluoride or zirconium fluorosilicate may be present in oral care products, our analysis only identified the presence of sodium fluoride, sodium monofluorophosphate, and stannous fluoride in mouthwashes.16,31 The influence of sodium fluoride is attributed to the release of free fluoride ions upon dissolution. Although fluoride demonstrates anticariogenic properties and aids in preventing dental caries,32 excessive ingestion can lead to dental and skeletal diseases.33 Previous studies have consistently reported sodium fluoride as the most frequently detected fluoride compound.17 Additionally, the exclusion of drug store and internet purchases in present study may have limited the inclusion of other fluoride compounds in the analysis.
Numerous studies have demonstrated that CHX, a bisbiguanide, prevents the accumulation of dental plaque and gingival disorders and has antimicrobial effects on a broad spectrum of microorganisms.34 Through its action on the cell wall, CHX disrupts the integrity of the cell membrane, leading to bacterial lysis. Its bacteriostatic and bactericidal properties contribute to the inhibition of biofilm formation and maturation. Through its action on the cell wall, CHX disrupts the integrity of the cell membrane, leading to bacterial lysis. Its bacteriostatic and bactericidal properties contribute to the inhibition of biofilm formation and maturation.35 It has been stated that 3.5 billion people in the world are affected by oral diseases and the most common of these is periodontitis.36 In a study conducted in Istanbul,37 around 62% of 500 participants in a broad age range were found to have periodontitis. According to the oral and dental health profile survey conducted in Turkey in 2021, the prevalence of caries in the 5-year-old group was 64%, and bleeding gums was 16.2%. The prevalence of caries in the 12-year-old group was 46.6%, the prevalence of gingival bleeding was 48.7%; and gingival bleeding in the 35-to-44 age group was reported as 70.8%.38 Despite the significant incidence of dental disorders in the Turkish population, the presence of CHX in only one of the mouthwashes in our study poses a serious impediment to the struggle against oral diseases. Although it is stated that the lower the CHX ratio of mouthwashes containing CHX, which can be used in concentrations ranging from 0.1% to 0.2%, the lower the rate of adhesion to the teeth, it is believed that mouthwashes with a CHX concentration of less than 0.1% cannot have an effective antiplaque effect.39 In our study, the concentrations of chlorhexidine found in the mouthwashes were in the range of 0.025% to 0.2%. Whilst CHX was present in a total of 8 mouthwashes, the specific concentration in one of the mouthwashes was not specified. CHX produces a significant shift in the salivary microbiome, resulting in decreased nitrite levels and increased acidity. Due to this change, the levels of glucose and lactate in saliva rise, whilst the pH and buffering capacity fall. As a result of these CHX-caused interactions, one of the detrimental effects of CHX is the transition of the oral environment into one where caries production might accelerate and cardiovascular diseases are observed.40 In contrast, multiple in vivo and in vitro experiments have demonstrated that mouthwashes containing CHX can exhibit antiviral activity against SARS-COV-2 in a similar range of doses. In these studies examining its antiviral efficacy, however, the impact is diminished when administered combined with povidone iodine.41 In terms of combined effect, CHX shows strong antifungal activity when used together with thymol42; 15.75% (n = 7) of the mouthwashes in the present study included thymol. Thymol, which is commonly employed in the dentistry profession, can be utilised as an antibacterial and protective varnish. Both of these products minimise the accumulation of bacterial plaque and alleviate gingival diseases.43 Moreover, these 2 substances may trigger hypersensitivity44 and persistent toxic diseases.45 According to a study that predicted various risk scenarios based on the likelihood that alcoholics would consume mouthwash during alcohol withdrawal syndrome, 30% of mouthwashes contain thymol, the most dangerous and toxic ingredient is ethanol, and thymol can induce metabolic acidosis with overexposure.45 In the present study, there is insufficient information regarding the specific type of alcohol contained in mouthwashes labeled as “alcohol.” The possibility that mouthwashes labeled as “alcohol” may contain ethyl alcohol is concerning from a public health perspective.
The majority of mouthwashes are either water or water-alcohol based. Due to alcohol, specific tastes and flavouring chemicals can be dissolved in mouthwash, the efficacy of certain therapeutic agents can be enhanced, and alcohol plays a supportive function in the treatment of oral illnesses.46 It has been stated that mouthwashes containing alcohol may be slightly better in terms of effectiveness than nonalcoholic ones47 or there may be no difference between them.48 In this context, the presence of alcohol in mouthwashes has been the subject of controversy, and the emerging view is debatable. It has been claimed by the case control studies that alcohol-containing mouthwashes may affect the oral soft tissues and increase the risk of oral cancer when compared to mouthwashes without alcohol.49 Although it is said that alcohol can cause burning mouth syndrome, in the same research it is suggested that alcohol-containing mouthwash use does not play a direct role in the development of this condition.50 In addition, the preferred type of alcohol may be important in these discussions on alcohol. In the above-mentioned studies, ethanol-derived alcohols were discussed. The absence of ethyl alcohol in some of the mouthwashes included in our study, along with explicit statements on some labels indicating “alcohol-free,” is a significant finding in terms of consumer health, and indeed, it is gratifying. Alcohol was observed as type unspecified (n = 3; 6.66%), benzyl alcohol (n = 6; 13.33%), and sugar alcohols, namely eucalyptol (n = 7; 15.55%), menthol (n = 14; 31.11%), and sorbitol (n = 21; 46.67%). It is not known whether the mouthwashes containing unspecified alcohol contain ethanol. Furthermore, methyl salicylate has been identified as an alcohol solvent (n = 6; 13.33%) and it has been stated in the scientific literature that this component may trigger severe toxicity45 and cardiac asystole.51 Benzyl alcohol is reported to be a safer and more benign material when compared to ethyl alcohol, suitable for use with a lower potential for harm on the body.52,53 Despite attempts to contact product managers of mouthwash brands containing alcohol to determine the type and percentage of alcohol in their products, sufficient information could not be obtained due to company policies and formula confidentiality; this is considered a limitation of the study. Fortunately, it is known that brands containing benzyl alcohol must comply with EU regulations and use less than 1% benzyl alcohol in their products.54 It has been reported that components such as methanol, ethanol, and isopropyl alcohol can be present in mouthwashes up to a maximum of 5%.
In contrast, although eucalyptol is antimicrobial, it may induce maternal or foetal damage.55 It has been reported that the use of mouthwash that contains alcohol can be detected in the breath. In order for drivers not to experience victimisation at traffic controls, individuals should report whether they use alcohol-containing personal care products.56 Sorbitol and menthol were frequently encountered amongst the mouthwashes in the present study; however, it could not be determined in the literature whether these agents cause any adverse effects. Sorbitol, one of the most prevalent sweeteners and humectants found in mouthwashes, has been utilised in foods and personal care products for decades.57 According to findings, sorbitol, which has a low glycaemic index and low caloric content, is also suitable for dental use.57 Menthol, on the other hand, is derived from Mentha arvensis and possesses antibacterial, analgesic, and stimulant qualities along with multiple therapeutic actions. It has also been found that it has antibacterial activity against many bacteria such as Staphylococcus aureus.58 In the current era where natural components are gaining prominence, the usage of such substances in oral treatments can be seen favourably. Many plant extracts are used in mouthwashes to minimise dental plaque accumulation and increase the number of oral bacteria. Consequently, herbal mouthwashes can provide the same advantages as mouthwashes containing CHX.59 There was no statistically significant difference in the effectiveness of herbal mouthwashes containing phytotherapeutic herbs, essential oils, and a large number of active components and conventional mouthwashes containing CHX.59,60 However, it was indicated that more clinical investigations should be conducted on this subject.60 Herbally, anti-inflammatory activity can be achieved by using essential oils in mouthwashes.61 Cistus species resin extract (n = 1; 2.22%) Mentha arvensis herb oil (n = 3; 6.66%), Quercus robur bark extract (n = 1; 2.22%), and cinnamal/cinnamon (n = 7; 15.55%) were detected in the present study as natural materials amongst the mouthwashes included. Cistus species contain polyphenols and, as a result, have antibacterial62 and antiviral properties.63 This therapeutic substance, which has been a component of traditional medicine in several regions of the world for many years, has demonstrated its efficacy against microbial infections through in vitro research.64 The antifungal agent cinnamal65 that acts on Candida albicans due to cinnamaldehyde and Quercus species produced from oak bark due to their high tannin content have been identified in the literature as an effective novel natural agent in periodontal treatment.36 The increased prevalence of these natural substances in oral care products will mitigate the detrimental effects of other synthetic items and the long-term negative consequences they may have on the human body.
Numerous food materials, cosmetics, and oral care products contain preservatives, which enhance the shelf life of the products. These ingredients are available both artificially and organically; nonetheless, artificial ingredients are preferred mostly.66 Although benzoic acid, paraben, and sorbate derivatives are commonly used in dental care products, it has been discovered that they may contribute to a variety of illnesses, including hypersensitivity, asthma, and cancer.66,67 In our study, preservative agents such as benzoic acid (n = 8; 17.77%), caprylyl glycol (n = 1; 2.22%), lactic acid (n = 3; 6.66%), o-cymene-5-ol (n = 1; 2.22%), potassium sorbate (n = 9; 20%), sodium metabisulfite (n = 1; 2.22%), butylated hydroxytoluene (BHT) (n = 1; 2.22%), and paraben derivatives (n = 13; 28.88%) were detected. Parabens, the most debated substance in recent years, is a preservative used in cosmetics and personal care items to prevent microbiological contamination. Although it is favoured because it is readily accessible, effective, and affordable, it poses harm to human health. However, not only in mouthwash but also in many personal care products, individuals are highly likely to encounter various types of parabens. These parabens can be systematically absorbed and can enter the body through the skin, being present in various body fluids and eventually excreted through these fluids, causing adverse effects on the environment as well.68,69 Methylparaben has the simplest structure, with back-to-back methyl groups; ethyl, propyl, and butylparaben can be derived from it.70 Methylparaben (n = 7; 15.55%) and propylparaben (n = 5; 11.11%) were identified in the present investigation. Whilst there is no information about the percentages of parabens in mouthwashes, in accordance with the standards of the European Union, methylparaben and ethylparaben are allowed to be used separately in personal care and cosmetic products at a maximum rate of 0.4%. If they are together, the maximum rate is 0.8%.70 It is important to remember that paraben derivatives can cause cancer by mimicking estrogen in the human body71 and are endocrine system disruptors.72 Although utilised as a synthetic antioxidant,73 since BHT is recognised as a potential endocrine disruptor, it has been suggested that BHT, which reduces transforming growth factor-ß1 release at repeated doses, should be present at a maximum dosage of 0.1% in dentifrices and 0.001% in mouthwashes.73 In recent years, O-cymene-5-ol, a natural chemical produced from isopropyl cresol, has been used to boost oral health in mouthwashes and toothpaste research.74,75 It is regarded as a multipurpose agent not only because it serves as a preservative17 but also because it provides antibacterial activity,75 reduces enamel demineralisation, and serves as an odourant.76 One of its positive aspects is that it provides tissue retention when applied to reconstructed gingival tissues.77
Different types of surfactant agents can be used in mouthwashes. In the present study, PEG-4 (n = 1; 2.22%), PEG-40 (n = 10; 22.22%), PEG-60 (n = 3; 6.66%), sodium methyl cocoyl taurate (n = 2; 4.44%), sodium lauryl sulfate (SLS) (n = 8; 17.77%), Poloxamer 338 (n:1; 2.22%), Poloxamer 407 (n:20; 44.44%), and polysorbate 20 (n = 5; 11.11%) were found. These chemicals, which may be anionic, cationic, or amphipathic, exert pressure on bacteria, reduce surface energy, and denature proteins by foaming and cleaning the surface.78,79 In vivo investigations have shown that SLS compounds induce cell damage, hair loss, skin and eye discomfort, and organ damage. It should also be mentioned that several countries accept the restricted use of SLS derivatives in a variety of personal care products.80, 81, 82 On the contrary, it has been established that SLS-like compounds are efficient in suppressing COVID-19 infection by inhibiting angiotensin-converting enzyme-2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), which are viral entry routes.83 Choosing mouthwash containing these substances is one technique for avoiding illness.84 According to prior research, more than 90% of examined mouthwashes include surfactants, and PEGylated agents are also popular.17 In personal care products, PEGylated oils serve as surfactants, emulsification, or solubilisation agents. In addition, they may serve as nonionic surfactants in oral, dermal, and parenteral delivery of drugs, and there are several oils with diverse PEG chain lengths.85 In research on gingival fibroblast cells, it was determined that the LC50 threshold for cytotoxicity of PEG-40 was close to 50% and that it lacked antibacterial action.86 It has also been suggested that PEG-40 generates less cytotoxicity when used alone than when combined with propylene glycol. In an in vivo investigation where PEG-40 was employed as the primary surfactant for oral nanoemulsion, PEG-400 was utilised as a cosurfactant, and it was reported that PEG-40 is a suitable and noncytotoxic substance for the transport of active drugs.87 It should not be ignored that this agent, which is neither cytotoxic nor antimicrobial on its own,86 can induce harmful effects with different chemical solvents, and studies in this direction should be developed. PEG-60, on the other hand, is a macromolecule greater than 1000 kDa in weight and is a water-insoluble material that has shown low oral acute toxicity in studies.88 Although polysorbate 20, a flavouring and solubilisation agent found in mouthwashes, has an absorption-enhancing effect in the gastrointestinal region in patients with difficult intestinal absorption of oral medication,89 it has been discovered that it can occasionally induce toxic effects due to increase intestinal permeability.90 Developments in the field of nanotechnology and polymers have led to the emergence of more specific target-oriented polymers such as poloxamer, which can exhibit evoked potentials and biological behaviour and can be used in drug delivery systems.91, 92, 93 These amphiphatic agents contribute to the targeting of drugs used in the treatment of microorganisms and infections such as C albicans,94 HIV,95 and S aureus.96 Poloxamer, of which there are several variants, was included in the majority of the mouthwashes in our sample. Poloxamer 338 was detected in only one mouthwash. Although some research have revealed that these polymers may induce subchronic or acute toxicity, the majority of animal and clinical trials has revealed no detrimental effects that are clinically significant.91
Polyvinyl methyl vinyl ether and maleic acid (PVM/MA) provide reducing dentine fluid flow in combination with arginine.97 This agent was rarely encountered in our study (n = 2; 4.44%). The copolymer of this ingredient has antibacterial properties and in combination with arginine98 is a biocompatibility agent that can reduce bacterial adhesion by increasing its effectiveness.99 The oral environment's pH and ion balance may be adjusted by combining PVM/MA copolymers with various treatments. When combined with arginine, the polymer of the 2 components is neutralised synergistically by the negative regions of arginine and inhibits dentin discomfort by drastically lowering dentin fluid flow.98 Despite the demonstration of such effectiveness in published studies, the absence of arginine in mouthwashes available on the market shelves in Turkey is perplexing for patients with dentin sensitivity and restricts the physician's recommendations. A large number of studies have been conducted, and the adverse effects of various types of PVM/MA copolymers have been examined. At the end of the review, it was stated that they can be used safely in cosmetic materials.100
Zinc components101 are vital for many organs and tissues in the human body and may serve as an antibacterial, antiplaque, and antiodour in the mouth. They can remove oral mucositis in patients with cancer undergoing chemotherapy and enhance the quality of life of patients.102,103 Zinc chloride, which can inhibit caries formation104 and suppress plaque accumulation105 by affecting the character of caries-forming flora in dental plaque, indirectly prevents weight loss in patients with oral mucositis.103 In addition, the presence of zinc ions inside oral cavity regulates the pH balance in the oral environment through enzymatic activity.106 Although it has been mentioned that zinc ions, which are involved in numerous enzymatic reactions for normal growth functions in the body, also function as antioxidants not only in the oral environment but also in the body, this mechanism has not been fully elucidated.107 Although it has been stated that zinc salts can be used safely in adult toothpastes and should not be included in dental care products for individuals younger than 6 years, no research has been conducted on mouthwashes this claim. Excessive zinc intake may induce some nerve damage due to neurologic adverse effects.108
For the certification of colour additives, US Food and Drug Administration (FDA) research chemists create and adjust both new and current analytical procedures. They also included to their research are the synthesis and characterisation of reference materials, the discovery of undiscovered impurities, and the introduction of new analytical techniques. For certification, inductively coupled plasma-mass spectrometry, quadrupole time-of-flight mass spectrometry, ultra-performance liquid chromatography, and others are used. In the present study, 8 different dye materials were identified, including Allura Red AC (CI 16035) (n = 4; 8.88%), Brilliant Blue FCF (CI 42090) (n = 8; 17.77%), Fast Green FCF (CI 42053) (n = 6; 13.33%), Sunset Yellow FCF (CI 15985) (n = 1; 2.22%), Tartrazine (CI 19140) (n = 7; 15.75%), Quinoline Yellow WS (CI 47005) (n = 4; 8.88%), Red 33 (CI 17200) (n = 5; 11.11%), Patent Blue V (Cl 42051) (n = 13; 28.88%), and Acid Orange 7 (CI 15510) (n = 1; 2.22%). Patent Blue V (Cl 42051) has been the most commonly found colour additive, and it was determined that 12 mouthwashes contained no dyes at all. In some mouthwashes (n = 13), multiple dye materials were detected, with one mouthwash reported to contain 4 different colour additives. Synthetic dyes may break down into the gastrointestinal system and produce different irritations and allergic responses due to the release of aromatic amines during digestion.109 Additionally, synthetic dyes may degrade the photostability of aqueous products. Components originating from the photodegradation of dyes that deteriorate over time may be detrimental to the oral mucosa, although more research is required. In this regard, Patent Blue V has a shorter half-life and degrades faster than Allura Red.110 Using high performance liquid chromatography (HPLC), Hasan et al111 expressed worry that the legal limit might be surpassed by consuming Sunset Yellow and Fast Green in combination with other food items. In addition, tartrazine112 may provoke sensitivity issues, urticaria, and asthma, whilst Allura Red113 may induce DNA damage. Also, Quinolin Yellow can cause tumour formation and allergenic or carcinogenic effects.114 Although its release from various foods has been examined by the HPLC test method and reported to be released below legal limits,115 there is no similar study on mouthwashes. Many types of mouthwashes containing dyes may cause discolouration, particularly in tooth-coloured composite materials, but it should not be neglected that, according to the research, mouthwashes have a minor influence on the colour stability of dental composites.116
When the contents of mouthwashes on the market and pharmacy were analysed, a substantial number of ingredients that might induce adverse reactions were discovered. Amongst the study's limitations is the time frame during which market data were obtained. From that time period to the present, the brands and models of the materials on the market shelves may have changed. Perhaps new materials have been brought in. This might also be considered a drawback, given that the research has evolved over time. Similarly, only the products seen on store shelves were examined in this investigation. To maintain consistency, agents that may be acquired online or in drugstores were excluded from the research. The inclusion of only mouthwashes accessible in an aqueous medium is another restriction of this research. Particularly, there were no tablet or powdered mouthwashes on the market shelves. In addition, the research excluded agents available as chewable tablets, saliva stimulants, foams, gels, and mouth sprays.
Conclusion
The purpose of the present study was to investigate the effects and intended usage of the ingredients included in commercially available mouthwashes as well as to identify any possible adverse impacts. According to the research on toothpaste,16 many compounds that might cause harmful effects and DNA and cell damage can also be ingested through mouthwash, hence boosting the body's concentration of these agents. It is crucial for human and environmental health that dental care products, which include various agents with hazardous effects, conduct research and development to purge themselves of these substances and make products based on this idea. Today, life expectancy is rising, people are paying more attention to their health as a result of social networks, and they are concerned with dental hygiene. Life expectancy has increased the amount of time that teeth remain in the mouth; thus, it is essential to optimise oral hygiene. People may thus prevent oral disorders such as dental caries and periodontitis by not only brushing their teeth but also employing other oral agents like mouthwash.
People can avoid the occurrence of oral diseases by utilising mouthwashes. However, mouthwashes alone are not as effective as using a toothbrush and toothpaste. In addition, individuals may lack enough awareness about the usage of mouthwashes. Although it is limited, there is research on the detrimental consequences of overuse. Therefore, the level of awareness about the use of mouthwash needs to be improved for both physicians and patients, and it is crucial to carry out some awareness-raising studies in this field. Additionally, clinicians should recognise the need of understanding and following the substance of mouthwashes.
Author contributions
Conceptualisation: O.Y. and M.K.U. Methodology: O.Y. Software: M.K.U and K.G. Validation: O.Y., M.K.U., and K.G. Formal analysis: M.K.U. Investigation: K.G. Resources: M.K.U and K.G. Data curation: K.G. Writing–original draft preparation: M.K.U. and K.G. Writing–review and editing: O.Y. Visualisation: M.K.U. Supervision: O.Y. Project administration: M.K.U.
Conflict of interest
None disclosed.
Footnotes
Supplementary material associated with this article can be found in the online version at doi:10.1016/j.identj.2023.08.004.
Appendix. Supplementary materials
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