Mouthwash controversies

Sir, in the current controversial discussion regarding the carcinogenic effects of alcohol-containing mouthwashes, the article by Werner and Seymour (BDJ 2009;  207: E19; summary BDJ 2009;  207: 488–489), along with the review on oral cancer by Warnakulasuriya (BDJ 2009;  207: 471–475) and related commentary (BDJ 2009;  207: 461), can be seen as a highlight in well-balanced and independent scientific discourse.^1, 2,3, 4 I fully agree with the conclusion to advise against the regular use of alcohol-containing oral products for reasons of precautionary public health protection, especially as sufficient alcohol-free alternatives are available.

Both articles^1, 3 discussed the perplexing inconsistencies among the review articles, which used the same original studies as their basis. Perhaps these inconsistencies are not so surprising if we refer to the conflicts of interest or financial disclosure of the articles, however. The McCullough and Farah article,⁵ which stated a cautious position, came from academia with no declared conflicts of interest. In contrast, the recent review by La Vecchia,⁶ which provided a negative outcome, was conducted with 'partial unconditioned support' from Johnson and Johnson Consumer (the current maker of Listerine-brand mouthwash). Especially interesting is the re-analysis by Cole et al.⁷ of the NCI dataset published by Winn et al.:⁸ while the original study concluded that there is a significantly increased risk of oral cancer associated with the regular use of mouthwash, the re-analysis found this association unlikely. Cole et al.'s study was financially supported by Warner-Lambert Company (the former maker of Listerine). As detected previously,⁹industry-supported reviews on ethanol appear to have more favourable conclusions than the corresponding independent studies.

Besides the industry bias issue, there is a considerable amount of knowledge on mechanistic evidence and quantitative risk assessment that was only briefly mentioned in the articles. While I agree that the risk of oral cancer from mouthwash use is difficult to quantify,¹ it is not completely impossible. We have recently shown that the use of alcohol-containing mouthwashes may lead to acetaldehyde concentrations in the oral cavity of up to 105 μM, which exceeds levels that have been shown in vitro to form DNA adducts and cause sister chromatid exchanges. A twice-daily use of alcohol-containing mouthwashes leads to a low but quantifiable lifetime cancer risk of 3E-6.¹⁰ The acetaldehyde burden may be increased by the cumulative exposure from a considerable number of other sources, which do not only include alcohol but also nutrition, flavourings, tobacco, and environmental exposures. The local carcinogenic effects of acetaldehyde in light of the cumulative exposure may be the molecular explanation for the link between mouthwash use and oral cancer detected in some of the epidemiological studies. It is notable that the International Agency for Research on Cancer recently upgraded acetaldehyde associated with alcohol consumption to group 1, with oesophagus, head, and neck as tumour sites with sufficient evidence for carcinogenicity in humans.¹¹Nevertheless, I agree with the editorial comment⁴ that the controversy around alcohol mouthwashes should not overshadow the far greater significance of alcohol drinking itself.