Download Opinion on hyrodogen peroxide in tooth whitening products

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[email protected]
From
Professor Philip Lamey, Professor of Oral Medicine and Oral Pathology
Professor Ruth Freeman, Professor of Dental Public Health, Epidemiology, Preventive Dentistry and
Paediatric Dentistry
Professor Martin Grootveld, Chemistry, London
Professor Edward Lynch, Professor of Restorative Dentistry and Gerodontology and Chairman of the
European Experts group on Tooth Whitening.
Peroxides have been used for tooth bleaching/whitening for more than 30 years. The safety and efficacy
of hydrogen peroxide and carbamide peroxide bleaching/whitening agents is well documented and there
are many different products (10 - 30% carbamide peroxide releasing 3.6 - 10% hydrogen peroxide)
currently available via dental offices. Tooth whitening products with varying levels of hydrogen peroxide
or hydrogen peroxide releasers (typically up to 10% hydrogen peroxide) are sold directly to consumers.
Based upon the published data, the International Agency for Research on Cancer (IARC) has concluded
that there is limited evidence in experimental animals for the carcinogenicity of hydrogen peroxide. IARC
stated that there was ‘inadequate evidence in humans for the carcinogenicity of hydrogen peroxide’,
despite the significant industrial exposure to this chemical and its widespread use5.
A critical analysis of the non-clinical data, including in vitro and in vivo genotoxicity, carcinogenicity and
tumour initiation-promotion studies, leads to the conclusion that exposure to hydrogen peroxide from the
use of tooth whitening product under recommended or exaggerated use conditions is not a significant risk
for the development of oral cancer.
A chemical that has a tumour-promoting action requires long-term, sustained high-dose exposure for
neoplastic lesions to develop. Without such exposure, lesions either fail to develop or regress1, 16. In
addition, such exposures generally produce clear evidence of tissue damage at the affected site (e.g.,
fore-stomach 2,3,12,15 and skin7). A pre-clinical study conducted to assess the toxicity of hydrogen
peroxide when administered orally in drinking water to mice with low catalase levels, demonstrated that
stomach and/or duodenum lesions regressed upon cessation of hydrogen peroxide treatment11.
Exposure to 30% hydrogen peroxide in a hamster buccal pouch assay12 failed to induce tumours despite
evidence of chronic inflammation. No visible pathological changes that could plausibly be related to
future preneoplastic or neoplastic lesion development were seen in any subjects in more than 100 clinical
trials with tooth whitening products. Any effects of hydrogen peroxide from tooth whitening products use,
even over 6-months of continuous exposure, are mild, transient, and involve only gingival irritation and
tooth sensitivity, both of which resolve within a few days after use of the product is stopped. These
studies, many of which have included smokers, provided no evidence to indicate that the rate or severity
of the adverse effects of tooth whitening products were significantly different from non-smokers. In
addition, concentrations of hydrogen peroxide achieved in the saliva in contact with the floor of the
mouth, one of the more common sites for oral cancers in the general population, are very low within 15
(0.0001%) to 60 (<0.00007%) minutes of the application of tooth whitening products9,10. The gingiva, in
contrast to the floor of the mouth, is a very rare site for the development of oral cancer.
A 7.5-year follow-up study on a small group of tooth whitening products users does exist in the scientific
literature8. During the exposure portion of this study subjects received 6-months of continuous hydrogen
peroxide treatment for tetracycline stains. No evidence of adverse effects in the oral cavity were noted in
9 of the 15 who agreed to a clinical examination, and none of the 15 participants in the study reported
any side effects that they believed to have been treatment-related.
Whilst hydrogen peroxide at high concentrations is weakly carcinogenic to the duodenum of mice that are
catalase deficient, peroxidase/catalase activity of saliva in humans would protect against the effects of
hydrogen peroxide in the oral cavity.
Increased cancer risk from combined exposures can arise when one exposure and other concomitant
exposures each convey a cancer risk. For example, combined smoking and asbestos exposures, which
individually present cancer risks4, 6, present greatly increased risks for lung cancer when exposure is
combined6. Since there is no established human cancer risk from tooth whitening products or hydrogen
peroxide, there is no basis to postulate that tooth whitening products would increase cancer risk in
smokers and/or heavy drinkers
Therefore, the results of initiation-promotion or combined exposure studies, cannot be extrapolated to
suggest a potential risk of hydrogen peroxide to the oral mucosa of heavy smokers and/or drinkers from
tooth whitening product under recommended, exaggerated or extended, conditions of use. This
conclusion is also supported by the fact that there are many common tumour promoters, including food
ingredients such as sodium chloride, butylated hydroxylanisole, glycerin, and sucrose, but no known
tumour promoter for the oral cavity7.
Reference list:
1. Burns, F.; Vanderlaan, M.; Sivak, A.; Albert, R. 1976. The regression kinetics of mouse skin
papillomas. Cancer Res 36(4):1422-1427.
2. da Costa Filho LC, da Costa CC, Sória ML, Taga R 2002. Effect of home bleaching and smoking on
marginal gingival epithelium proliferation : a histologic study on woman. J Oral Pathol Med 31: 473480.
3. Grasso, P.; Sharratt, M.; Cohen, A.J. 1991. Role of persistent, non-genotoxic tissue damage in
rodent cancer and relevance to humans. Annu Rev Pharmacol Toxicol 31:253-287.
4. IARC. 2003. Predictive Value of Rodent Forestomach and Gastric Neuroendocrine Tumors in
Evaluating Carcinogenic Risk to Humans. International Agency for Research on Cancer (IARC):
Lyon, France. IARC Technical Publication No.39.
5. IARC. 2002. Tobacco Smoking And Tobacco Smoke. International Agency for Research on
Cancer (IARC): Lyon, France. IARC Monographs on the Evaluation of Carcinogenic Risks to
Humans, Vol. 83.
6. IARC. 1999. Hydrogen peroxide. In: Re-Evaluation of Some Organic Chemicals, Hydrazine and
Hydrogen Peroxide. [IARC Working Group Meeting], Feb. 17-24, 1998, Lyon, France. International
Agency for Research on Cancer (IARC); Lyon, France. IARC Monographs on the Evaluation of
Carcinogenic Risks to Humans, Vol. 71, Part 2, pp. 671-689.
7. IARC. 1977. Asbestos. International Agency for Research on Cancer (IARC); Lyon, France. IARC
Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 14.
8. Kraus, A.L.; Munro, I.C.; Orr, J.C.; Binder, R.L.; LeBoeuf, R.A.; Wiliams, G.A. 1995. Benzoyl
peroxide: An integrated human safety assessment for carcinogenicity. Regul Toxicol Pharmacol
21(1):87-107.
9. Leonard, R.H. (Jr.); Van Haywood, B.; Caplan, D.J.; Tart, N.D. 2003. Nightgaurd vital bleaching of
tetracycline-stained teeth: 90 months post treatment. J Esthet Restor Dent 15(3):142-152.
10. Mahony, C.; Barker, M.L.; Engel, T.M.; Walden, G.L. 2003. Peroxide degradation kinetics of a
direct application percarbonate bleaching film. Am J Dent 16 Spec No:9B-11B.
11. Slezak, B.; Santarpia, P.; Xu, T.; Monsul-Barnes, V.; Heu, R.T.; Stranick, M.; Sullivan, R.; Petrou, I.;
Bagley, D.; Li, Y. 2002. Safety profile of a new liquid whitening gel. Compend Contin Educ Dent
23(11, Suppl. 1):4-11.
12. Weiner ML, Freeman C, Trochimowicz H, de Gerlache J, Jacobi S, Malinverno G, Mayr W, Regnier
JF. 2000. 13-week drinking water toxicity study of hydrogen peroxide with 6-week recovery period in
catalase-deficient mice. Food Chem Toxicol 38:607-615.
13. Weitzman, S.A.; Weitberg, A.B.; Stossel, T.P. 1986. Effects of hydrogen peroxide on oral
carcinogenesis in hamsters. J Periodontol 57(11):685-688.
14. Wester, P.W.; Kroes, R. 1988. Forestomach carcinogens: pathology and relevance to man.
Toxicol Pathol 16(2):165-171.
15. Williams, G.M.; Whysner, J. 1996. Epigenetic carcinogens: Evaluation and risk assessment. Exp
Toxicol Pathol 48(2&3):189-195.
16. Wurtzen, G. 1993. Scientific evaluation of the safety factor for the acceptable daily intake (ADI).
Case study: butylated hydroxyanisole (BHA). Food Addit Contam 10(3):307-314.
This paper represents the views of its author on the subject. These views have not been adopted or in any way approved by the Commission
and should not be relied upon as a statement of the Commission's or Health & Consumer Protection DG's views. The European Commission
does not guarantee the accuracy of the data included in this paper, nor does it accept responsibility for any use made thereof.