R. Periodontia - Setembro 2008 - Volume 18 - Número 03 PRODUTOS QUÍMICOS EM ENXAGUATÓRIOS COMERCIALIZADOS EM CAMPINAS, BRASIL Chemicals in commercial mouthwashes available in Campinas, Brazil Kleber Leilsson dos Santos1, Camila Oliveira Lopes1, José Carlos Morais de Oliveira1, Raquel Soares Binotti2, Celso Henrique de Oliveira1 RESUMO Esse estudo teve por objetivo avaliar os diferentes componentes químicos de enxaguatórios comercializados na cidade de Campinas/SP. Dezessete produtos foram analisados. O estudo demonstrou um total de 82 produtos químicos diferentes, relacionados em 195 citações. Os produtos químicos mais prevalentes foram anti-sépticos, conservantes, aditivos, corantes e produtos derivados de plantas. O presente estudo mostrou que vários componentes químicos presentes na formulação dos enxaguatórios podem contribuir para o aparecimento de reações adversas e sensibilização em humanos. UNITERMOS: Enxaguatório; Mentha piperita; Saúde Bucal; Higiene Bucal. R Periodontia 2008; 18:46-51. 1 INTRODUCTION Mouthwashes are commonly used to keep the mouth clean and smelling fresh, and are prescribed by dentists and physicians for treating halitosis, gingivitis, recurrent aphthous ulcers, and prevention of dental caries (Marsh, 1992; Barrons, 2001; Drisko, 2001; FDI Commission, 2002). These products became progressively available for purchase in Brazil in recent years. However, little information is available about the most important chemicals in these products, as well, the differences among them. Mouthwashes can be constituted by several chemicals such as antiseptics, preservatives, additives, dyes, sweeteners, and solvents. Despite being considered safe and effective, mouthwashes can cause many adverse effects and human sensitization (Gar vey et al, 2007; Morken & Gjerdet, 2006; Krautheim et al, 2004; Soo Hoo et al, 2003). The aim of this study was to analyze the chemicals present in mouthwashes commercially available in Brazil, commonly used for mouth hygiene by children and adults. School of Medicine, São Francisco University – USF – Bragança Paulista (SP), Brazil School of Medicine, State University of Campinas – UNICAMP – Campinas (SP), Brazil Recebimento: 16/04/08 - Correção: 18/06/08 - Aceite: 28/07/08 46 MATERIAL AND METHODS Seventeen different commercially available products were purchased in stores in Campinas, São R. Periodontia - 18(3):46-51 Table 1 LIST OF MOUTHWASHES PURCHASED IN CAMPINAS - SP, BRAZIL Trade Name 1 2 ® Malvona Scope ® ® Industry Country Lot # Vol. (ml) Laboratório Primá Brazil 1103H02 100 Procter & Gamble US NA 250 Kolynos do Brasil Brazil 09 250 3 Plax 4 Anapyon® DM Indústria Farmacêutica Brazil 503 100 5 Malvatricin® Laboratório Daudt Oliveira Brazil 30304 100 Kolynos do Brasil Brazil 12 250 6 7 Kolynos ® ® Dental Fresh Kley Hertz Brazil 3010 300 8 ® Cepacol Aventis Pharma Brazil 302202 300 9 Listerine® Warner-Lambert US 02433L 250 10 Tom and Jerry® Johnson & Johnson Brazil 01 250 Gillette Argentina Argentine Y-140-2 350 Laclede US 84175 250 Biolab Sanus Farmacêutica Brazil 302590 240 Kolynos do Brasil Brazil 10 250 Kolynos do Brasil Brazil 09 250 Johnson & Johnson Brazil 03 250 Sonae Distribuição Brasil Brazil 07B03D 250 11 12 13 Oral-B ® ® Biotene Fluotrat ® ® 14 PerioGard 15 Sorriso Herbal® 16 Fluordent® 17 ® Enxaguatório Bucal Big NA = not available Paulo/Brazil, from September to October, 2003. All chemicals described in mouthwash labels were listed and discussed. The data were analyzed by descriptive statistics. RESULTS Table 1 presents a list of 17 mouthwashes. Their labels showed 82 different chemicals, a total of 195 citations. The Chemicals prevalence among the total of citations on labels from mouthwashes are presented in Figure 1. Interestingly, the most frequently obser ved chemicals listed were antiseptics and/or preservatives, herbally derived compounds, additives, and dyes [Tables 2 to 4]. A median of 12 chemicals was observed for each product. Furthermore, the average and the standard deviation were 11.5 ± 4.5 chemicals for product (ranging from 2 to 16 chemicals). In one case, the product label listed only 2 chemicals (product #7); neither the solvent(s) nor the aroma described in front-label as ‘Strong Peppermint’ were listed as compounds. This fact shows that information on chemicals listed on labels of mouthwashes may be incomplete. Herbally derived compounds were obser ved in 12 different mouthwashes (70.6%). An average of 1.8 herbal derived chemicals were observed per product (range of 0 to 6 and median of 1). Eleven different plants were listed. The most prevalent was Peppermint (Mentha piperita), representing 48.4% of herbal citations. In addition, 11 products (64.7%) had Peppermint-derived compounds in their composition (not included the product # 7 – see the previous paragraph). Eucalyptus (Eucalyptus globulus) was also habitually cited, representing 12.9% of herbal derived compounds. Less Figure 1 - Chemicals prevalence among the total of citations on labels from mouthwashes (%) 47 R. Periodontia - 18(3):46-51 Table 2 LIST OF CHEMICALS DESCRIBED IN LABELS FROM 17 MOUTHWASHES PURCHASED IN BRAZIL Chemicals + % Acidulating / Alkalizing Agents Chemicals + % Antiseptics / Preservatives Sodium phosphate monobasic 4 23.5 Cetylpyridinium chloride 7 41.2 Citric acid 2 11.8 Sodium benzoate 5 29.4 Lactic acid 1 5.9 Benzoic acid 3 17.6 Sodium hidroxide 1 5.9 Methylparaben 3 17.6 Propylparaben 3 17.6 Additives Sodium fluoride 7 41.2 EDTA disodium 2 11.8 Sorbitol 6 35.3 Tyrothricin 2 11.8 Starch 1 5.9 Triclosan 2 11.8 Zinc gluconate 1 5.9 Sodium borate 1 5.9 Sodium lactate 1 5.9 Domiphen bromide 1 5.9 Lactoferrin 1 5.9 Chlorhexidine digluconate 1 5.9 Sodium methyltaurate 1 5.9 Chinosol 1 5.9 Povidone 1 5.9 Thymol 1 5.9 Sweeteners Surfactants Saccharin sodium 10 58.8 Poloxamers 402 or 407 4 23.5 Xylitol 2 11.8 Polysorbates 20 / 80 3 17.6 Sodium cyclamate 1 5.9 Sodium lauryl sulfate 2 11.8 Sucralose 1 5.9 Pluronic F-108 or F-127 2 11.8 Copolymer 1 5.9 Emulsifiers Glycerin 9 52.9 Polyoxyl 40 stearate 1 5.9 Disodium phosphate 6 35.3 Surfon R-400 1 5.9 Sorbitan laurate 1 5.9 Others Aroma 4 23.5 Enzymes Glucose oxidase 1 5.9 Methyl salicylate 2 11.8 Lactoperoxidase 1 5.9 Tannic acid 1 5.9 Lysozyme 1 5.9 Benzocaine 1 5.9 Zinc chloride 1 5.9 Solvents Water 15 88.2 Fenosalil 1 5.9 Ethanol 11 64.7 Hydrolized 1 5.9 Propylene glycol 1 5.9 Ethyl hydroxyethyl cellulose 1 5.9 (+) = number of products in which the chemical was listed. Dyes and herbally derived chemicals not included. popular plants such as Erva-de-Bugre (Casearia sylvestris) were also listed. Table 4 shows the plants listed on mouthwash labels. DISCUSSION In conjunction with regular tooth cleaning, over-the48 counter mouthwashes are dental care products that can be used to treat halitosis, gingivitis, periodontitis, recurrent aphthous ulcers, and for dental caries prevention (Marsh, 1992; Barrons, 2001; Drisko, 2001; FDI Commission, 2002). In intensive care units, oral decontamination with 2% chlorhexidine solution for the prevention of ventilator- R. Periodontia - 18(3):46-51 Table 3 Table 4 LIST OF DYES DESCRIBED IN LABELS FROM 17 PREVALENCE OF HERBALLY DERIVED COMPOUNDS DESCRIBED MOUTHWASHES PURCHASED IN BRAZIL. Dyes IN LABELS FROM 17 MOUTHWASHES PURCHASED IN BRAZIL. Present in ‘n’ Products % Herbal Citations Present in ‘n’ Products % Blue (CI 42090) 7 41.2 Yellow (CI 19140) 5 29.4 Peppermint (Mentha piperita) 11 64.7 Red (CI 16035) 2 11.8 Yellow (CI 15985) 1 5.9 Eucalyptus (Eucalyptus globulus) 4 23.5 Blue (CI not available) 1 5.9 Clove (Syzygium aromaticum) 2 11.8 Caramel (CI not available) 1 5.9 High Mallow (Malva sylvestris) 2 11.8 Green (CI 42053) 1 5.9 Aloe (Aloe vera) 1 5.9 Red (CI 17200) 1 5.9 Chamomile (Matricaria chamomilla) 1 5.9 Chinese Cinnamon (Cinnamomum cassia) 1 5.9 Erva-de-Bugre (Casearia sylvestris) 1 5.9 Tea Tree (Melaleuca alternifolia) 1 5.9 Myrrh (Commiphora spp.) 1 5.9 Salvia (Salvia officinalis) 1 5.9 CI = International Colour Index (The Merck Index, 2003) associated pneumonia showed to be significantly effective (Tantipong et al, 2008). In recent years, mouthwash use has increased in Brazil. Despite the fact that their use can generally be considered safe, few studies have evaluated the adverse effects of mouthrinsing (Moghadam et al, 1991; Gagari & Kabani, 1995). Adverse or allergic events after mouthwash use are considered to be rare. However, several adverse events have already been described after mouthwashing, such as angioedema, anaphylaxis, skin rash, urticaria, or contact dermatitis (Garvey et al, 2007; Morken & Gjerdet, 2006; Krautheim et al, 2004; Moghadam et al, 1991; Gagari & Kabani, 1995). Phenolic compound (such as eucalyptol, menthol, and thymol) toxicity was suspected to be associated to a case of fatal large-volume mouthwash ingestion (Soo Hoo et al, 2003). The present study reviewed that several chemicals present in mouthwashes can contribute to adverse effects and sensitization, with the most prevalent chemicals being antiseptics, preser vatives, additives, and dyes. These chemicals are recognized to be frequently related to human sensitivity and irritant lesions in skin and mucous membranes (Garvey et al, 2007; Guin, 1995). Herbal compounds were habitually listed mouth-rinse labels. Many studies have studied the effect of herbal compounds in oral diseases such as gingivitis and gingival bleeding, or as an antimicrobial agent (Walker, 1988; Wennstrom, 1988; Kaim et al, 1998; Pistorius et al, 2003). A double-blind, placebo controlled, parallel-study with 40 healthy adult volunteers showed that Herbal Mouth and Gum Therapy significantly reduced gingivitis and gingival bleeding scores compared to the control group (Scherer et al, 1998). Finally, it is noteworthy that products # 2, 6, 8, 15, and 16 listed the dye tartrazine (CI 19140) in their composition as requested by the newer Government Resolution RE #572 (re-published in April, 4th 2002). This Resolution requests that labels must inform the consumer that tartrazine can lead to allergic reactions (Agência Nacional de Vigilância Sanitária, 2004). CONCLUSION The study showed that mouthwashes are quite different in their chemical composition. Antiseptics and preservatives were the most frequently obser ved chemicals. Herbally derived compounds (mainly from Peppermint), additives, and dyes are also common. Several chemicals present in mouthwash formulas can contribute to adverse effects and human sensitization to mouthwashes. ABSTRACT The aim of this study was to investigate chemicals in commercial mouthwashes purchased in the city of Campi49 R. Periodontia - 18(3):46-51 nas/SP. Seventeen different mouthwashes were analyzed. The study showed a total of 82 different chemicals listed on labels with 195 citations. The most prevalent chemicals listed were antiseptics, preservatives, additives, dyes, and herbal related compounds. The present study showed that several chemicals present in mouthwash formulas can contribute to adverse effects and human sensitization to mouthwashes. UNITERMS: Mouthwashes; Mentha piperita; Oral health; Oral hygiene REFERENCES 1- Agência Nacional de Vigilância Sanitária [homepage on the Internet]. Brasília, DF: Ministério da Saúde: ANVISA; 2004 [cited 2004 Nov 13]. [1 screen]. Available from: URL: http://www.anvisa.gov.br/legis/resol/ 2002/572_02re.htm report and review of the literature. Contact Dermatitis 2004;50:1136. 10- Marsh PD. Microbiological aspects of the chemical control of plaque and gingivitis. J Dent Res 1992; 71:1431-8 2- Barrons RW. Treatment strategies for recurrent oral aphthous ulcers. Am J Health Syst Pharm 2001; 58:41-50 3- Drisko CH. Nonsurgical periodontal therapy. Periodontol 2000 2001; 25:77-88 4- FDI Commission. Mouthrinses and periodontal disease. Int Dent J 2002; 52:346-52 11- Moghadam BK, Drisko CL, Gier RE. 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Mouthrinses in “experimental gingivitis” studies. J Clin Periodontol 1988; 15:511-6 Endereço para correspondência: Celso Henrique de Oliveira Av. Orosimbo Maia, 570 - 51 CEP: 13010-918 – Campinas - SP, Brazil Phone: + 55 (19) 3233-5319 Fax number: + 55 (19) 3236-5759 E-mail: [email protected] 51