From Volume 43, Issue 8, October 2016 | Pages 728-733
There have been numerous reports in the scientific literature investigating the possible association between alcohol-containing mouthwashes and oral cancer but relatively few epidemiological surveys have taken place and the findings have been equivocal. This article will address the controversial issue of the safety of mouthwashes and provide an objective assessment of the latest scientific evidence.
Although mouthwashes are marketed to benefit the oral health of patients, there is the potential for harmful side-effects as a result of using these products. In the first article in this series the local unwanted side-effects from active ingredients in mouthwashes have been discussed, including staining of the teeth and oral soft tissues, taste disturbance, increased calculus formation, and mucosal erosion. The rare reports of parotid enlargement and anaphylactic response to the use of chlorhexidine-containing mouthwashes were also raised. In the past 20 years, there has been a marked increase in the availability and use of ‘over the counter’ low alcohol and alcohol-free mouthwashes. However, a number of mouthwashes containing higher concentrations of alcohol are marketed as anti-plaque products. The concentration of alcohol varies from around 5% to 27%. Alcohol is added to mouthwashes to act as a solvent for other constituents and for taste purposes. Above concentrations of 10–12%, it also acts as a preservative, antiseptic and as an anti-plaque agent enhancer.1 Ethanol at high concentration (18–27%) enhances the effect of essential oils.2
There has been a limited number of reports of acute systemic toxicity in children as a result of swallowing alcohol-containing mouthwashes (ACM).3,4 This paper will focus on the possible chronic harmful effects of ACM when used as recommended by the manufacturer.
For the past 35 years there have been numerous reports in the scientific literature investigating the possible association between ACM and oral cancer, but relatively few epidemiological surveys have taken place and the findings have been equivocal.2 Some studies have found an association between ACM use and oral cancer and others have found no increased risk.1,2,5,6,7,8 Such evidence that exists is difficult to interpret owing to both avoidable and unavoidable flaws in study design.1,2,5,6,7,8,9 These include:
One study has addressed the issue of validation of mouthwash use questionnaire responses with particular reference to alcohol exposure from mouthwashes.10 It was found that, of those that used mouthwashes, the majority used mouthwashes containing alcohol (61%) but that lifetime exposure from alcohol in mouthwashes was small. Of the subjects that used ACM, 68% had rinsed with the equivalent of a glass of wine (175 ml 12% proof, equivalent to two units of alcohol) per day for six months and a further 11% for less than a year; 11% had rinsed with this amount for more than three years. This sample was a subset of the Pilot Study of the Grampian Adult Dental Health Survey, which included questions on oral health (including mouthwash use).11 A total of 480 subjects were invited to participate and 300 (63%) responded.11 Of these, 161 agreed to further contact and 132 participants were invited to complete the mouthwash alcohol exposure questionnaire; 73 (55%) responded. This illustrates the difficulty of collecting self-reported data in epidemiological studies.10
A systematic literature search and meta-analysis of epidemiological studies of mouthwash use, in particular high alcohol-containing mouthwashes, and oral cancer risk was conducted in 2012 following the MOOSE guidelines (meta-analysis of observational studies).2 Using standard inclusion criteria, 12 studies provided sufficient information to be included in the meta-analysis and another four were included in the sensitivity analyses. The authors found no statistically significant increased risk of oral cancer from the regular use of mouthwashes or from increased use during the day. More specifically, no association was found between use of mouthwashes containing high levels of alcohol and risk of oral cancer.2
Arguably, this meta-analysis provides the most reliable evidence available that ACMs are safe.2 However, it has been suggested that this meta-analysis may have been ‘doomed to failure’ from the start.12 Pure alcohol has not been shown to be carcinogenic, although it has been shown to increase the permeability of the oral mucosa to tobacco-specific nitrosamines. A biological mechanism whereby ethanol is converted into its toxic metabolite, acetaldehyde, within the oral cavity could explain an increased risk of oral cancer with alcohol-containing mouthwash use. Lachenmeier and co-workers have investigated the lifetime risk of oral cancer from twice daily use of an ACM based on the acetaldehyde exposure in saliva (also including acetaldehyde exposure from other cosmetic products). They used the methodology of the EU's scientific committee on cosmetic products and non-food products intended for consumers. They found that the increased risk would result in three to four cases per million of the population.13 The largest study in the meta-analysis contained 918 cases and 2752 controls and a combination of the participants in all the studies: 4,484 cases and 8,781 controls.2,6 These numbers would not have the power to detect such a low risk. For this reason, it can be argued that it is unlikely that it will ever be possible to detect the risk posed by ACMs epidemiologically, even employing the most sophisticated statistical methodology; the confounding effects of smoking and consumption of alcoholic beverages have the same carcinogenic mechanism, that is exposure of the oral mucosa to acetaldehyde.12
Two studies have recently reported that mouthwash use in general (both alcohol-containing and alcohol free) is a risk factor for oral cancer.7,8 In the first study, this was due to the effect of alcohol-free mouthwash use as alcohol-containing mouthwashes showed only a weak association with pharyngeal cancer and no association with cancer of the oral cavity.7 This finding may have been spurious because only eight cases and 14 controls were using low or no alcohol-containing mouthwashes frequently.7 In the second study only subjects who used mouthwashes three or more times daily had an increased risk of oral cancer and those that used mouthwashes according to the manufacturer's instructions had no increased risk.8 This was one of the largest case-control studies (1963 cases and 1993 controls) ever conducted into the causes of upper aerodigestive tract cancer in relation to oral hygiene habits and dental care. It had strict inclusion critieria and careful adjustment for multiple confounding factors.8 However, no information on the reason for the frequent use of mouthwashes was available and it has been suggested that this may have been to reduce symptoms from other oral disorders, including halitosis and discomfort.9 This could have biased the results as poor oral health has been shown to be independently associated with oral cancer.8,14,15 Alternatively, increased mouthwash use could have been associated with the presence of undiagnosed oral cancer rather than the cause of it.8,9 It is also possible that synergistic interactions between excessive mouthwash use and smoking, alcohol and poor oral hygiene increased the risk of oral cancer and these interactions should be considered in future statistical models.13
The most effective method of disruption of the plaque biofilm is mechanical. Although the risk of oral cancer from the use of ACMs is likely to be small, it could contribute to the acetaldehyde cumulative load in the oral cavity from other sources, not only including alcoholic beverages but also foodstuff, flavourings, tobacco and environmental factors.16 In addition, low pH may increase the toxicity of mouthwashes and the effect of low pH on acetaldehyde toxicity is an area which requires further investigation.13 Most antiseptic mouthwashes can only reduce plaque formation not inhibit it. The only mouthwashes on the market which can prevent plaque formation, when used in the correct formulation and dosage, are those containing chlorhexidine gluconate.17 The clinical applications of chlorhexidine-containing mouthwashes have been described in part one of this series. Chlorhexidine has a limited effect on established plaque and some undesirable side-effects. Other formulations of mouthwashes are only around half as effective at reducing plaque formation. Therefore mouthwashes can never substitute for effective toothbrushing and interproximal cleaning (Figure 1).
For the vast majority of the population the focus of personalized oral hygiene information and demonstration should be complete removal of plaque using mechanical methods. An enhanced oral hygiene behaviour change strategy (Oral Hygiene TIPPS) was described in the recent guidance document on The Prevention and Treatment of Periodontal Diseases in Primary Care published by The Scottish Dental Clinical Effectiveness Programme (SDCEP) (Figure 2). For those patients who wish to rinse with a mouthwash for that ‘fresh mouth feeling’ an alcohol-free, fluoride-containing one, used as prescribed by the manufacturer, may be recommended. There is evidence of a beneficial effect of fluoride-containing mouthwashes in combination with toothbrushing on coronal and root caries.18,19,20,21,22,23 The guidance document can be downloaded free of charge from the SDCEP website (www.sdcep.org.uk).
