16. US FDC Reports. The Tan Sheet. 10 June 1996. 17. US Department of Health and Human Services. Food and Drug Administra- tion. Federal Register 2003;68:32241– 32243. SEBASTIAN G. CIANCIO New York, USA (Received 29 January 2009.) ALCOHOL-CONTAINING MOUTHWASHES: AUTHORS’ REPLY We thank Dr Ciancio for his inter- est in our review article and would like to respond to several aspects he has raised in his Letter to the Editor. The review article that Dr Cian- cio presents as evidence of the lack of epidemiological support for the role of alcohol-containing mouthwashes in the development of oral cancer is from ‘‘Den- tal Health’’ which is the British Society of Dental Hygiene and Therapy’s scientific journal. This journal is not available to non- members, is not available via PubMed, is not listed on Dentistry 2000 (http://www.dentistry2000. com/dentaljournals) and may well be not peer reviewed. Thus, it is impossible to meaningfully com- ment on this review article and their conclusions. Dr. Ciancio demonstrates that the amount of alcohol consump- tion shown to be associated with oral mucosal changes is in the order of 15 g per day for 15 years. However, he does not consider the fact that there may well be a topical effect of alcohol. Pure ‘‘ethanol’’ (alcohol) is not used for human consumption (at least that we are aware of, and definitely not for oral hygiene practice). We apologize for not mentioning in our review article the hamster cheek study reported in 1984 showing the lack of adverse effect of short-term (30-day) applica- tion of alcohol. It is the long- term, synergistic effect that topical alcohol and smoking has on the oral mucosa that our review focused upon. Many of the arguments that Dr Ciancio presents in the bullet points of his letter are, in effect, repetitions of the arguments sup- plied by Professor Walsh in the March edition of the ADJ. 1 We feel that we have extensively dis- cussed these arguments in our reply to Professor Walsh’s letter in that edition of the ADJ. To briefly summarize our response: • We feel that there is growing evidence that alcohol can have a topically, rather than systemic, role in oral carcinogenesis. • It is extremely difficult to assess co-factors in clinical and epide- miological research where there is an overwhelming significant principle factor (smoking) invol- ved in the aetiology of a dis- ease. If there is an indication that there is a compounding, synergistic association, then this link should be assessed in an unbiased fashion, and brought to the attention of the oral health profession so that they can make an informed decision. • There is growing evidence of not only an epidemiological link, but also laboratory evidence, to support an association between the long-term use of alcohol- containing mouthwash in the development of oral cancer. Dr Ciancio goes on to discuss, at length, the proposition that acetaldehyde (formed by the breakdown of alcohol) is safe and not of concern. He presents the 1988 study by Til et al. that showed acetaldehyde in rats’ drinking water after 4 weeks did not result in any adverse outcome to the rats, as well as the United States of America Environment Protection Agency’s statement on acetaldehyde. This latter state- ment (correctly linked as: http:// www.epa.gov/iris/subst/0290.htm) was last revised in 1991, was an assessment of the carcino- genic potential of inhaled (not topical) acetaldehyde, and con- cludes by classifying acetal- dehyde inhalation as ‘‘probable human carcinogen … based on increased incidence of nasal tumors in male and female rats and laryngeal tumors in male and female hamsters after inhalation exposure’’. There is now increasing evi- dence that acetaldehyde is a mutagen and carcinogen accord- ing to numerous in vitro cell cul- ture studies and in vivo animal models 2 as well as being asso- ciated with alcohol-related gastro- intestinal tract carcinogenesis. 3 Epidemiologic studies on Asian heavy drinkers with impaired acetaldehyde metabolism due to aldehyde dehydrogenase-2 deficiency strongly suggest that acetaldehyde is a topical carcino- gen. 4 This deficiency results in the accumulation of acetaldehyde locally in the saliva during ethanol metabolism 5 and also in markedly increased risk for many upper gastrointestinal tract cancers. 6–8 Thus, these studies provide strong evidence for the topical carcino- genic role of acetaldehyde in the upper gastrointestinal tract in humans. Dr Ciancio asks the interesting question of ‘‘how potent is the affect of acetaldehyde as a car- cinogen?’’ and we would suggest that, from evidence presented, it would appear to be very potent. A further question raised by Dr Ciancio is the possibility that alcohol and acetaldehyde are not present for long enough periods of time in the oral cavity to cause any long-term harm. He uses the interesting analogy of dental caries (although we believe that the pathological process of dental caries and oral cancer are dra- matically different) and readily Letters to the Editor 182 ª 2009 Australian Dental Association