Abstracts

INTRODUCTION

Toothbrushing with fluoride toothpastes has been pointed out as one of the factors responsible for the decline in dental caries in high³3 Bratthall D, Hänsel-Petersson G, Sundberg H. Reasons for the caries decline: what do the experts believe? Eur J Oral Sci. 1996;104(4 Pt 2):416-22. DOI:10.1111/j.1600-0722.1996.tb00104.x and medium-income countries, such as Brazil.¹⁰10 Cury JA, Tenuta LMA, Ribeiro CCC, Paes Leme AF. The importance of fluoride dentifrices to the current dental caries prevalence in Brazil.Braz Dent J. 2004;15(3):167-74. DOI:10.1590/S0103-64402004000300001 Besides that, the use of toothpastes may be considered the most rational method of fluoride use, because at same time that brushing promotes dental biofilm (dental plaque) disorganization, fluoride concentration is increased in the oral cavity.¹²12 Cury JA, Tenuta LMA. How to maintain a cariostatic fluoride concentration in the oral environment. Adv Dent Res. 2008;20(1):13-6. DOI:10.1177/154407370802000104 Nonetheless, fluoride must be chemically compatible in the toothpaste formulation to ensure anti-caries efficacy.³⁰30 Tenuta LMA, Cury JA. Laboratory and human studies to estimate anticaries efficacy of fluoride toothpastes. In: Van Loveren C, editor. Toothpastes. Basel: Karger; 2013. p.108-24. (Monographs in Oral Science, 23).

Systematic reviews concluded that toothpaste formulations must contain concentrations of at least 1,000 ppm fluoride to provide an anti-caries effect.²¹21 Marinho VC, Higgins JP, Sheiham A, Logan S. Fluoride toothpastes for preventing dental caries in children and adolescents. Cochrane Database Syst Rev. 2003;(1):CD002278. DOI:10.1002/14651858.CD002278^,3131 Walsh T, Worthington HV, Glenny AM, Appelbe P, Marinho VC, Shi X. Fluoride toothpastes of different concentrations for preventing dental caries in children and adolescents. Cochrane Database Syst Rev. 2010;(1):CD007868. DOI:10.1002/14651858.CD007868.pub2 Moreover, to be able to interfere with the caries process, reducing demineralization and enhancing dental remineralization, fluoride must be chemically soluble in the formulation.¹²12 Cury JA, Tenuta LMA. How to maintain a cariostatic fluoride concentration in the oral environment. Adv Dent Res. 2008;20(1):13-6. DOI:10.1177/154407370802000104 Therefore, fluoride concentration and stability has been studied since the early 1980s. Those analyses have confirmed that not all toothpastes are able to maintain, until their expiration dates, the minimum soluble fluoride concentration required to yield maximum anti-caries effect.¹⁰10 Cury JA, Tenuta LMA, Ribeiro CCC, Paes Leme AF. The importance of fluoride dentifrices to the current dental caries prevalence in Brazil.Braz Dent J. 2004;15(3):167-74. DOI:10.1590/S0103-64402004000300001^,1313 Cury JA, Oliveira MJL, Martins CC, Tenuta LMA, Paiva SM. Available fluoride in toothpastes used by Brazilian children. Braz Dent J. 2010;21(5):396-400. DOI:10.1590/S0103-64402010000500003^,1515 Dantas EDV, Romão DA, Nóbrega DF, Velo MMAC, Pereira CM, Tenuta LMA, et al. Prazo de validade e concentração de flúor solúvel nos dentifrícios mais vendidos no Brasil [abstract]. Braz Oral Res. 2013;27 Suppl 1:311.^,2828 Ricomini Filho AP, Tenuta LMA, Fernandes FSF, Calvo AFB, Kusano SC, Cury JA. Fluoride concentration in the top-selling Brazilian toothpastes purchased at different regions. Braz Dent J. 2012;23(1):45-8. DOI:10.1590/S0103-64402012000100008^,aa Cortes G, Gomes JFF, Rebelo MAB, Cury JA. Potencial anticárie dos dentifrícios distribuídos pelo Serviço Público de Saúde Bucal no Município de São Gabriel da Cachoeira, AM, Brasil. In: Anais do 10º Congresso Brasileiro de Saúde Coletiva; 14-18 nov 2012; Porto Alegre, Brasil. Brasília (DF): ABRASCO; 2013.

The Brazilian regulation about fluoride in toothpastes has underwent several modifications, which abolished the requirement that fluoride is soluble in the formulation.^bb Ministério da Saúde, Secretaria Nacional de Vigilância Sanitária. Portaria nº 22, de 20 de dezembro de 1989. Diario Oficial Uniao. 22 dez 1989; Seção II:241.^,cc Ministério da Saúde, Agência Nacional de Vigilância Sanitária. Portaria nº 108, de 26 de setembro de 1994. Diario Oficial Uniao. 28 set 1994; p.14704.^,dd Ministério da Saúde, Agência Nacional de Vigilância Sanitária. Portaria nº 71, de 29 de maio de 1996. Aprova a relação de documentos necessários à formação de processos para autorização, alteração e cancelamento de funcionamento de empresa, registro de produto, suas alterações, revalidação, cancelamento e outros procedimentos afins, conforme anexos I, II, III, IV, V, VI, VII, VIII, IX e X e dá outras providências. Diario Oficial Uniao. 4 jun 1996; p.9821-3.^,ee Ministério da Saúde, Agência Nacional de Vigilância Sanitária. Portaria nº 79, de 28 de agosto de 2000. Diario Oficial Uniao. 30 ago 2000; p.1415-1537. Thus, the current regulation in Brazil (ANVISA, Regulation 79) only establishes that total fluoride (F) concentration in toothpaste must not be higher than 0.15% (1,500 ppm F).^ee Ministério da Saúde, Agência Nacional de Vigilância Sanitária. Portaria nº 79, de 28 de agosto de 2000. Diario Oficial Uniao. 30 ago 2000; p.1415-1537. Therefore, since this legislation was published, toothpastes with less 1,000 ppm of soluble F, or having most fluoride chemically insoluble, have been found in the market.²2 Benzian H, Holmgren C, Palesnstein Helderman W. Efficacy of fluoride toothpaste over time [letter to editor]. Braz Dent J. 2012;23(4):311-4. DOI:10.1590/S0103-64402012000400001^,2525 Orth RM, Assaf AV, Zanin L, Mialhe FL, Klein ALL, Medina MRJ, et al. Concentração de flúor nos principais dentifrícios comercializados no Brasil e impacto da nova portaria de regulamentação. Rev Odonto Cienc.2001;16(32):27-33. The same problem has been shown with fluoride toothpastes distributed by public health care services to socially vulnerable populations.^aa Cortes G, Gomes JFF, Rebelo MAB, Cury JA. Potencial anticárie dos dentifrícios distribuídos pelo Serviço Público de Saúde Bucal no Município de São Gabriel da Cachoeira, AM, Brasil. In: Anais do 10º Congresso Brasileiro de Saúde Coletiva; 14-18 nov 2012; Porto Alegre, Brasil. Brasília (DF): ABRASCO; 2013.

Thus, we evaluated how adequate the current Brazilian regulation governing fluoride toothpastes is.

METHODS

A bibliographical survey was conducted, regarding the period between 1981 and 2014, in the following electronic databases: LILACS, Medline, and SciELO. The following keywords were used: Dentifrices, Toothpastes, Fluoride, and Brazil, in the Portuguese and English languages.

Papers were selected based on the following criteria: peer-reviewed studies (descriptive, observational, intervention, and literature reviews), that had been fully published in scientific journals. Titles and abstracts were used for initial selection, according to the previously defined criteria.

A form was drafted to collect the following information from fully read, selected articles: title of the article, title of the periodical, year of publication, study country, category of the study (original, review, and others), theoretical reference, method of analysis, objective, and results found.

Official documents from the Brazilian Ministry of Health were also referred to, as well as the Brazilian and international regulations on fluoride toothpastes.

RESULTS ANALYSIS

Dental caries decline and the importance of fluoride toothpastes

Tooth decay is a cumulative disease that affects individuals of all ages and socioeconomic levels at different extents. It is more prevalent in economically and educationally vulnerable populations.²²22 Narvai PC, Frazão P, Castellanos RA. Declínio na experiência de cárie em dentes permanentes de escolares brasileiros no final do século XX. Rev Odontol Soc. 1999;1(1/2):25-9.^,2323 Narvai PC, Frazão P, Roncalli AG, Antunes JLF. Cárie dentária no Brasil: declínio, iniqüidade e exclusão social. Rev Panam Salud Publica. 2006;19(6):385-93. DOI:10.1590/S1020-49892006000600004 Even though caries indexes have significantly declined since the 1990s,^ff Ministério da Saúde, Secretaria de Atenção à Saúde, Departamento de Atenção Básica, Coordenação Nacional de Saúde Bucal. Projeto SB Brasil 2003: condições de saúde bucal da população brasileira 2002-2003: resultados principais. Brasília (DF); 2004 [cited 2015 Apr 30]. Available from: https://www.nescon.medicina.ufmg.br/biblioteca/imagem/1720.pdf ^,gg Ministério da Saúde, Secretaria de Atenção à Saúde; Secretaria de Vigilância em Saúde. SB 2010: Pesquisa Nacional de Saúde Bucal: resultados principais. Brasília (DF); 2012 [cited 2015 Apr 30]. Available from: http://bvsms.saude.gov.br/bvs/publicacoes/pesquisa_nacional_saude_bucal.pdf it remains one of the biggest public health problems in Brazil.²³23 Narvai PC, Frazão P, Roncalli AG, Antunes JLF. Cárie dentária no Brasil: declínio, iniqüidade e exclusão social. Rev Panam Salud Publica. 2006;19(6):385-93. DOI:10.1590/S1020-49892006000600004 Among factors contributing to that decline, besides the decentralization in the Brazilian health care system and the fluoridation of its public water supplies, the widespread use of fluoride toothpastes stands out.¹⁰10 Cury JA, Tenuta LMA, Ribeiro CCC, Paes Leme AF. The importance of fluoride dentifrices to the current dental caries prevalence in Brazil.Braz Dent J. 2004;15(3):167-74. DOI:10.1590/S0103-64402004000300001^,2222 Narvai PC, Frazão P, Castellanos RA. Declínio na experiência de cárie em dentes permanentes de escolares brasileiros no final do século XX. Rev Odontol Soc. 1999;1(1/2):25-9.^,2323 Narvai PC, Frazão P, Roncalli AG, Antunes JLF. Cárie dentária no Brasil: declínio, iniqüidade e exclusão social. Rev Panam Salud Publica. 2006;19(6):385-93. DOI:10.1590/S1020-49892006000600004

In fact, the implication of fluoride toothpastes to caries decline in most high³3 Bratthall D, Hänsel-Petersson G, Sundberg H. Reasons for the caries decline: what do the experts believe? Eur J Oral Sci. 1996;104(4 Pt 2):416-22. DOI:10.1111/j.1600-0722.1996.tb00104.x and medium-income¹⁰10 Cury JA, Tenuta LMA, Ribeiro CCC, Paes Leme AF. The importance of fluoride dentifrices to the current dental caries prevalence in Brazil.Braz Dent J. 2004;15(3):167-74. DOI:10.1590/S0103-64402004000300001 countries has been highlighted. The reduction of dental caries, regardless of public water supply fluoridation, is known to coincide with the implementation and more widespread use of those products.²⁷27 Petersson HG, Bratthall D. The caries decline: a review of reviews. Eur J Oral Sci. 1996;104(4):436-43. DOI:10.1111/j.1600-0722.1996.tb00110.x Similarly, it has been shown that dental caries declined in 16 countries at the same time that fluoride was added to over 90.0% of marketed toothpastes.²⁴24 Nishigawa M, Moriki D, Watanabe T. Relation between market share of fluoride dentifrices and caries reduction. J Dent Res. 1996;76 Spec Iss:193.

Particularly in Brazil, only 25.0% of toothpastes in the market were fluoridated until 1988. By then, no regulation existed in Brazil governing fluoride amounts in those products. In September 1988, fluoride was added to the top-selling toothpaste in Brazil, which had a market share of 50.0%. Thus, in 1989, the sale of fluoride toothpastes was widespread to a population scale in the country, and from there reached 90.0% of toothpaste sales.⁸8 Cury JA. Dentifrícios fluoretados no Brasil. RGO (Porto Alegre). 1989;37(2):139-42. That fact represented an expressive increase in access to fluoride in public health care, as Brazil ranks third regardingper capita toothpaste consumption, following only the United States and Japan.¹⁰10 Cury JA, Tenuta LMA, Ribeiro CCC, Paes Leme AF. The importance of fluoride dentifrices to the current dental caries prevalence in Brazil.Braz Dent J. 2004;15(3):167-74. DOI:10.1590/S0103-64402004000300001Besides that increase, both in the supply and in the consumption of fluoride toothpastes, the sanitary reform that took place in Brazil led to the implementation of health care prevention programs at schools, allowing for another segment of society to also be benefited by such fluoride use.¹⁰10 Cury JA, Tenuta LMA, Ribeiro CCC, Paes Leme AF. The importance of fluoride dentifrices to the current dental caries prevalence in Brazil.Braz Dent J. 2004;15(3):167-74. DOI:10.1590/S0103-64402004000300001 This fact may have represented a strong impact in dental caries reduction in Brazilian school-children, regardless of water fluoridation.¹⁰10 Cury JA, Tenuta LMA, Ribeiro CCC, Paes Leme AF. The importance of fluoride dentifrices to the current dental caries prevalence in Brazil.Braz Dent J. 2004;15(3):167-74. DOI:10.1590/S0103-64402004000300001^,2626 Pereira AC, Cunha FL, Meneghim MC, Werner CW. Dental caries and fluorosis prevalence study in a nonfluoridated Brazilian community: trend analysis and toothpaste association. ASDC J Dent Child. 2000;67(2):132-5,83.

The importance of fluoride toothpastes for the decline in dental caries rates that took place in Brazil has leveled off the impact of water fluoridation in the reduction of dental caries, as observed in other countries. As a matter of fact, Pereira et al²⁶26 Pereira AC, Cunha FL, Meneghim MC, Werner CW. Dental caries and fluorosis prevalence study in a nonfluoridated Brazilian community: trend analysis and toothpaste association. ASDC J Dent Child. 2000;67(2):132-5,83. (2000) followed the changes in dental caries prevalence in school-children from two municipalities, from 1991 to 1997. One of those municipalities had fluoridated water (Piracicaba, SP, Southeastern Brazil) and the other one did not (Iracemapolis, SP). In 1991, caries prevalence was 50.0% smaller in Piracicaba than in Iracemapolis. However, that percentage was gradually reduced with time, until it reached approximately 30.0% in 1997. That difference could have been even smaller if dental caries prevalence in Piracicaba was not also declining.

Nevertheless, in order that for fluoride toothpastes present anticaries potential, some minimum requirements must be met.

Composition and stability of fluoride toothpastes

Toothpaste formulations have several components, and each of them has a specific role to ensure the desired cosmetic and preventive-therapeutic effects.⁹9 Cury JA. Dentifrícios: como escolher e como indicar. In: Associação Paulista dos Cirurgiões-Dentistas. Odontologia. São Paulo: Artes Médicas - Divisão Odontológica, 2002. p.281-95. However, two of them must be discussed in further depth, having in mind their significant role in the caries control-activity of fluoride toothpastes: the abrasives and fluoride as preventive-therapeutic agent.¹⁴14 Cury JA, Tenuta LMA. Evidence-based recommendation on toothpaste use. Braz Oral Res. 2014;28 Spec Nº:1-7. DOI:10.1590/S1806-83242014.50000001^,2020 Lippert F. An introduction to toothpaste: its purpose, history and ingredients. In: Van Loveren C, editor. Toothpastes. Basel: Karger; 2013. p.1-14. (Monographs in Oral Science, 23).

Regarding the preventive-therapeutic components, toothpastes should contain available fluoride (chemically-soluble fluoride) in their formulas to have anti-caries effect. In order to achieve that, the types of abrasives in formulas and the chemical forms of fluoride used must be considered.¹⁴14 Cury JA, Tenuta LMA. Evidence-based recommendation on toothpaste use. Braz Oral Res. 2014;28 Spec Nº:1-7. DOI:10.1590/S1806-83242014.50000001 In fact, the first toothpastes that were developed in the 1960s were not fully effective in reducing dental caries, because the toothpaste was formulated with an abrasive and a fluoride salt that were chemically imcompatible.²⁰20 Lippert F. An introduction to toothpaste: its purpose, history and ingredients. In: Van Loveren C, editor. Toothpastes. Basel: Karger; 2013. p.1-14. (Monographs in Oral Science, 23).

In Brazil, most toothpastes in the market are manufactured with two kinds of fluoride salts: sodium monofluorophosphate (MFP = Na₂FPO₃) or sodium fluoride (NaF).²⁸28 Ricomini Filho AP, Tenuta LMA, Fernandes FSF, Calvo AFB, Kusano SC, Cury JA. Fluoride concentration in the top-selling Brazilian toothpastes purchased at different regions. Braz Dent J. 2012;23(1):45-8. DOI:10.1590/S0103-64402012000100008NaF is an inorganic salt that, in contact with water, releases fluoride as ion (F^-). In MFP, fluoride is covalently bound to the phosphorous atom and when it is dissolved, monofluorophosphate ions (FPO₃^2-) are released to the solution. Fluoride as F^- or FPO₃^2- ions released from NaF or MFP are potentially active against caries. NaF or MFP are added to toothpastes formulation depending on the abrasive systems used.⁹9 Cury JA. Dentifrícios: como escolher e como indicar. In: Associação Paulista dos Cirurgiões-Dentistas. Odontologia. São Paulo: Artes Médicas - Divisão Odontológica, 2002. p.281-95.^,2020 Lippert F. An introduction to toothpaste: its purpose, history and ingredients. In: Van Loveren C, editor. Toothpastes. Basel: Karger; 2013. p.1-14. (Monographs in Oral Science, 23). The proper combination of fluoridated compound and abrasive systems is fundamental to ensure that the toothpaste is effective against caries.²⁰20 Lippert F. An introduction to toothpaste: its purpose, history and ingredients. In: Van Loveren C, editor. Toothpastes. Basel: Karger; 2013. p.1-14. (Monographs in Oral Science, 23).

Regarding abrasive agents, they are important components in toothpastes, as they control tooth staining and help remove accumulated biofilm from the teeth during brushing. In Brazil, most toothpastes that are used by the population have calcium carbonate (CaCO₃) as their abrasive agent.²⁸28 Ricomini Filho AP, Tenuta LMA, Fernandes FSF, Calvo AFB, Kusano SC, Cury JA. Fluoride concentration in the top-selling Brazilian toothpastes purchased at different regions. Braz Dent J. 2012;23(1):45-8. DOI:10.1590/S0103-64402012000100008 In other countries, dicalcium phosphate dihydrate (CaHPO₄.2H₂O) is also used as abrasive.²⁰20 Lippert F. An introduction to toothpaste: its purpose, history and ingredients. In: Van Loveren C, editor. Toothpastes. Basel: Karger; 2013. p.1-14. (Monographs in Oral Science, 23). Those toothpastes containing calcium in the abrasive have free Ca⁺⁺ ions in their formulas, which react with ionic fluoride, forming into the toothpaste tube calcium fluoride-like (CaF₂) insoluble salts, which do not have anticaries property.¹⁴14 Cury JA, Tenuta LMA. Evidence-based recommendation on toothpaste use. Braz Oral Res. 2014;28 Spec Nº:1-7. DOI:10.1590/S1806-83242014.50000001

Thus, toothpastes containing Ca in their abrasives cannot be formulated with NaF, SnF₂ or amine fluorides salts because fluoride ions present in them immediately react with Ca⁺⁺, forming insoluble salts.¹⁴14 Cury JA, Tenuta LMA. Evidence-based recommendation on toothpaste use. Braz Oral Res. 2014;28 Spec Nº:1-7. DOI:10.1590/S1806-83242014.50000001^,2020 Lippert F. An introduction to toothpaste: its purpose, history and ingredients. In: Van Loveren C, editor. Toothpastes. Basel: Karger; 2013. p.1-14. (Monographs in Oral Science, 23). Since insoluble fluoride salts do not have anticaries effect, silica (SiO₂) has been used as an abrasive agent in toothpastes that are formulated with fluoride salts that produce fluoride ions. Toothpastes formulated with SiO₂ allow that all fluoride added remain soluble throughout shelf life of the toothpaste.¹⁴14 Cury JA, Tenuta LMA. Evidence-based recommendation on toothpaste use. Braz Oral Res. 2014;28 Spec Nº:1-7. DOI:10.1590/S1806-83242014.50000001

As fluoride ion-generating salts cannot be used in toothpaste formulations containing Ca in their abrasives, MFP was developed in the 1960s, and it has been used in toothpastes ever since.²⁰20 Lippert F. An introduction to toothpaste: its purpose, history and ingredients. In: Van Loveren C, editor. Toothpastes. Basel: Karger; 2013. p.1-14. (Monographs in Oral Science, 23). As fluoride is covalently bound to phosphate, it does not immediately react with Ca⁺⁺ when toothpastes are produced. However, with time, MFP undergoes hydrolysis and releases fluoride ions, which react with Ca⁺⁺ ions of the abrasive. According to the time of storage, the concentration of soluble fluoride is gradually reduced and consequently the concentration of insoluble fluoride is increased in formulation containing MFP/CaCO₃.²⁹29 Tabchoury CPM, Cury JA. Estudo de condições de envelhecimento precoce de dentifrícios para prever o comportamento de flúor em condições ambientais. Rev Bras Farm. 1994;75(3):67-71. This fact reinforces the need for evaluating the shelf lives of toothpaste formulations and the availability of soluble fluoride in toothpastes in the market.¹⁴14 Cury JA, Tenuta LMA. Evidence-based recommendation on toothpaste use. Braz Oral Res. 2014;28 Spec Nº:1-7. DOI:10.1590/S1806-83242014.50000001

Fluoride concentration in Brazilian toothpastes

Both total and soluble fluoride concentrations in Brazilian toothpastes have been evaluated since the early 1980s.⁶6 Cury JA, Guimarães LOC, Arbex ST, Moreira BHW. Análise de dentifrícios fluoretados: concentração e formas químicas de fluoretos encontrados em produtos brasileiros. Rev APCD. 1981;35(2):142-7. At that time, seven fluoride toothpastes existed in the Brazilian market and only two of them had proper soluble fluoride concentration to have anticaries potential. The evaluation of stability of Brazilian fluoride toothpastes was first conducted in the early 1980s and published in 1986.⁷7 Cury JA. Estabilidade do flúor nos dentifrícios brasileiros. RGO (Porto Alegre). 1986;34(5):430-2. The results showed that only three of seven toothpastes analyzed had totally stable fluoride. Insoluble fluoride concentration increased with time in four toothpastes and after a year at room temperature, in one toothpaste only 20.0% of soluble fluoride was found. Thus, this study showed that Brazilian fluoride toothpastes had very different stability patterns, indicating possibly impaired anticaries effect.

In 1989, fluoride concentrations in 10 toothpastes of the Brazilian market were determined when they were purchased (fresh samples) and after accelerated aging.⁸8 Cury JA. Dentifrícios fluoretados no Brasil. RGO (Porto Alegre). 1989;37(2):139-42. The results showed that only 40.0% of toothpastes had stable fluoride in their formulations. In the remaining toothpastes, insoluble fluoride percentage increased with time, ranging from 10.0% to 80.0%. These results indicated the need to regulate the quality of fluoride toothpastes in Brazil.

Ten years later, Duarte et al (1999) reported the fluoride concentration and stability in the five top-selling toothpastes in Brazil from the five regions of the country.¹⁶16 Duarte FF, Pisaneschi E, Cury JA. Avaliação do flúor dos dentifrícios mais consumidos no Brasil e comercializados nas cinco regiões do país. Rev ABOPREV.1999;2(2):3-10. The results showed that soluble fluoride concentrations in fresh samples were smaller than expected, decreasing by 21.0% and 44.0% after the accelerated aging process. The only toothpaste that maintained its soluble fluoride concentration with time was the one containing silica (SiO₂) as abrasive. The authors¹⁶16 Duarte FF, Pisaneschi E, Cury JA. Avaliação do flúor dos dentifrícios mais consumidos no Brasil e comercializados nas cinco regiões do país. Rev ABOPREV.1999;2(2):3-10. concluded that part of fluoride was not chemically available in the most toothpastes evaluated, impairing their anticaries potential effect.

Orth et al²⁵25 Orth RM, Assaf AV, Zanin L, Mialhe FL, Klein ALL, Medina MRJ, et al. Concentração de flúor nos principais dentifrícios comercializados no Brasil e impacto da nova portaria de regulamentação. Rev Odonto Cienc.2001;16(32):27-33. (2001) described fluoride concentration in the five top-selling toothpastes in Brazil and in one that had been launched in the market soon after Resolution 79 from ANVISA (August 28, 2000) had become effective.^ee Ministério da Saúde, Agência Nacional de Vigilância Sanitária. Portaria nº 79, de 28 de agosto de 2000. Diario Oficial Uniao. 30 ago 2000; p.1415-1537. Five had MFP/CaCO₃ and one had MFP/SiO₂ in their formulations. The data showed that in only one of the toothpastes all fluoride was soluble. In the remaining ones, insoluble fluoride percentages ranged from 6.0% to 55.0%. In the newly-launched toothpaste, total fluoride concentration was 1,423 ppm F, which complied with the recently launched regulation. However, it only had 635 ppm of soluble F to provide anticaries effect. Therefore, the authors concluded that it was mandatory to review ANVISA's regulation to ensure population access to toothpastes containing fluoride potentially active against dental caries.

Fluoride stability was evaluated in seven toothpastes sold in Manaus, AM, under distinct environmental conditions. Five of them had MFP/CaCO₃ and two of them had NaF/SiO₂ in their formulations.⁵5 Conde NCO, Rebelo MAB, Cury JA. Evaluation of the fluoride stability of dentifrices sold in Manaus, AM, Brazil. Pesq Odontol Bras. 2003;17(3):247-53. DOI:10.1590/S1517-74912003000300009 The analyses showed that all evaluated toothpastes had soluble fluoride concentrations suitable to have anticaries potential. However, most toothpastes did not show fluoride stability after storage. In some of them, 40.0% of insoluble fluoride was found after 12 months storage at room temperature. The authors⁵5 Conde NCO, Rebelo MAB, Cury JA. Evaluation of the fluoride stability of dentifrices sold in Manaus, AM, Brazil. Pesq Odontol Bras. 2003;17(3):247-53. DOI:10.1590/S1517-74912003000300009 concluded that, although total fluoride concentrations in all toothpastes evaluated complied with Resolution 79 from ANVISA,^ee Ministério da Saúde, Agência Nacional de Vigilância Sanitária. Portaria nº 79, de 28 de agosto de 2000. Diario Oficial Uniao. 30 ago 2000; p.1415-1537. the reduction of soluble fluoride concentration during storage could impair anticaries effects of some formulations.

In 2010, Cury et al¹³13 Cury JA, Oliveira MJL, Martins CC, Tenuta LMA, Paiva SM. Available fluoride in toothpastes used by Brazilian children. Braz Dent J. 2010;21(5):396-400. DOI:10.1590/S0103-64402010000500003 analyzed 30 toothpaste brands that were being used by 206 Brazilian children from Montes Claros, MG, Southeastern Brazil. The study found that around 36.0% of MFP/CaCO₃-based toothpastes had less than 1,000 ppm of soluble fluoride in their composition.

Ricomini et al²⁸28 Ricomini Filho AP, Tenuta LMA, Fernandes FSF, Calvo AFB, Kusano SC, Cury JA. Fluoride concentration in the top-selling Brazilian toothpastes purchased at different regions. Braz Dent J. 2012;23(1):45-8. DOI:10.1590/S0103-64402012000100008 (2012) analyzed the five top-selling fluoride toothpastes in Brazil, which were purchased in the five regions of the country. Four had MFP/CaCO₃ and one had NaF/SiO₂ in their formulations. The authors showed that the five evaluated toothpastes had soluble fluoride concentrations greater than 1,000 ppm F, regardless of the regions where they were purchased. Nonetheless, when fluoride concentration in those toothpastes were evaluated after they have been stored at room temperature, only one of them was able to maintain soluble fluoride concentrations above 1,000 ppm F.¹⁵15 Dantas EDV, Romão DA, Nóbrega DF, Velo MMAC, Pereira CM, Tenuta LMA, et al. Prazo de validade e concentração de flúor solúvel nos dentifrícios mais vendidos no Brasil [abstract]. Braz Oral Res. 2013;27 Suppl 1:311.

All previous publications reporting the problem with fluoride concentrations in toothpastes involved products that had been purchased in the Brazilian market. Conversely, Cortes et al^aa Cortes G, Gomes JFF, Rebelo MAB, Cury JA. Potencial anticárie dos dentifrícios distribuídos pelo Serviço Público de Saúde Bucal no Município de São Gabriel da Cachoeira, AM, Brasil. In: Anais do 10º Congresso Brasileiro de Saúde Coletiva; 14-18 nov 2012; Porto Alegre, Brasil. Brasília (DF): ABRASCO; 2013. (2012) analyzed the fluoride concentrations in two toothpastes that were distributed by public oral health care services in Sao Gabriel da Cachoeira municipality, AM, Northern Brazil, to the local indigenous population. Both had formulas with total concentrations of 1,500 ppm F. However, the average soluble fluoride concentration in one of the toothpastes was 694.7 ppm F, while in the other it was 243.9 ppm F, both below the minimum 1,000 ppm F required to ensure anticaries effect. One of those toothpastes was commercial but the other one was distributed by the Brasil Sorridente (Smiling Brazil) program, an initiative from the Ministry of Health.

Thus, the results found confirm the need for revising the current Resolution 79 from ANVISA,^ee Ministério da Saúde, Agência Nacional de Vigilância Sanitária. Portaria nº 79, de 28 de agosto de 2000. Diario Oficial Uniao. 30 ago 2000; p.1415-1537. to ensure the population has access to fluoride toothpastes with anticaries effect.

Evolution and necessity to review the Brazilian regulation on fluoride toothpastes

The first Brazilian regulation on fluoride toothpastes was established in 1989, Regulation 22 of Secretaria Nacional de Saúde de Vigilância Sanitária(National Health Surveillance System).^bb Ministério da Saúde, Secretaria Nacional de Vigilância Sanitária. Portaria nº 22, de 20 de dezembro de 1989. Diario Oficial Uniao. 22 dez 1989; Seção II:241. That regulation established maximum and minimum soluble fluoride concentration parameters a toothpaste should have. Thus, when they were manufactured (fresh sample), toothpastes were required to have a soluble fluoride concentration of at least 1,100 ppm F and a maximum one of 1,500 ppm F. This regulation also established the minimum soluble fluoride concentrations that a toothpaste should maintain during its whole shelf life. That regulation underwent several changes, and it was superseded by later regulations from ANVISA (Table).^cc Ministério da Saúde, Agência Nacional de Vigilância Sanitária. Portaria nº 108, de 26 de setembro de 1994. Diario Oficial Uniao. 28 set 1994; p.14704.^,dd Ministério da Saúde, Agência Nacional de Vigilância Sanitária. Portaria nº 71, de 29 de maio de 1996. Aprova a relação de documentos necessários à formação de processos para autorização, alteração e cancelamento de funcionamento de empresa, registro de produto, suas alterações, revalidação, cancelamento e outros procedimentos afins, conforme anexos I, II, III, IV, V, VI, VII, VIII, IX e X e dá outras providências. Diario Oficial Uniao. 4 jun 1996; p.9821-3.^,ee Ministério da Saúde, Agência Nacional de Vigilância Sanitária. Portaria nº 79, de 28 de agosto de 2000. Diario Oficial Uniao. 30 ago 2000; p.1415-1537.

Regulation 108 from December 26, 1994^cc Ministério da Saúde, Agência Nacional de Vigilância Sanitária. Portaria nº 108, de 26 de setembro de 1994. Diario Oficial Uniao. 28 set 1994; p.14704. kept the same specifications as Regulation 22 concerning fluoride concentration and stability that a toothpaste should have when manufactured and throughout its shelf life. However, it did not specify that the concentration of fluoride in ppm should be soluble. Thus, this regulation would be attended even if all fluoride in a toothpaste with 1,500 ppm of total fluoride were insoluble (therefore without anticaries potential).

In 1996, a new regulation was drafted (Regulation 71 from May 29, 1996).^dd Ministério da Saúde, Agência Nacional de Vigilância Sanitária. Portaria nº 71, de 29 de maio de 1996. Aprova a relação de documentos necessários à formação de processos para autorização, alteração e cancelamento de funcionamento de empresa, registro de produto, suas alterações, revalidação, cancelamento e outros procedimentos afins, conforme anexos I, II, III, IV, V, VI, VII, VIII, IX e X e dá outras providências. Diario Oficial Uniao. 4 jun 1996; p.9821-3. It established that toothpastes should contain concentrations of 0.15% of fluoride (1,500 ppm F). The specification about fluoride stability was abolished but with no requirement that fluoride should be chemically soluble in the formulation. That regulation also specified that several fluoride salts could be used in toothpastes.

Resolution 79, from August 28, 2000 is currently in force in Brazil.^ee Ministério da Saúde, Agência Nacional de Vigilância Sanitária. Portaria nº 79, de 28 de agosto de 2000. Diario Oficial Uniao. 30 ago 2000; p.1415-1537. It regulates oral and dental hygiene products. Regarding fluoride toothpaste, that resolution only determines that the maximum fluoride concentration in formulas should not exceed 0.15% (expressed as fluoride – 1,500 ppm F). It also specifies the various fluoride salts that can be used in toothpastes. Nevertheless, that regulation does not determine how much soluble fluoride (potentially active against caries) a toothpaste should contain and maintain throughout its shelf life.

The information reported above suggests that, with the evolution of Brazilian regulations on fluoride toothpastes, the main concern was safety, because the legislations only specified the maximum total fluoride amount of 0.15% that a formulation should contain. Therefore, the current regulation does not ensure that fluoride is soluble in a toothpaste to have anti-caries potential. In several publications an appeal was made to change this regulation,⁵5 Conde NCO, Rebelo MAB, Cury JA. Evaluation of the fluoride stability of dentifrices sold in Manaus, AM, Brazil. Pesq Odontol Bras. 2003;17(3):247-53. DOI:10.1590/S1517-74912003000300009^,1010 Cury JA, Tenuta LMA, Ribeiro CCC, Paes Leme AF. The importance of fluoride dentifrices to the current dental caries prevalence in Brazil.Braz Dent J. 2004;15(3):167-74. DOI:10.1590/S0103-64402004000300001^,2525 Orth RM, Assaf AV, Zanin L, Mialhe FL, Klein ALL, Medina MRJ, et al. Concentração de flúor nos principais dentifrícios comercializados no Brasil e impacto da nova portaria de regulamentação. Rev Odonto Cienc.2001;16(32):27-33.^,2828 Ricomini Filho AP, Tenuta LMA, Fernandes FSF, Calvo AFB, Kusano SC, Cury JA. Fluoride concentration in the top-selling Brazilian toothpastes purchased at different regions. Braz Dent J. 2012;23(1):45-8. DOI:10.1590/S0103-64402012000100008 and the present publication systematically ratifies this necessity.

The problem discussed in this review is not only found in Brazil, because the legislations of other countries also do not ensure that toothpastes have minimum soluble fluoride concentration to have anticaries potential, as seen in international publications.¹1 Benzian H, Holmgren C, Buijs M, Loveren C, Weijden F, Palenstein Helderman W. Total and free available fluoride in toothpastes in Brunei, Cambodia, Laos, the Netherlands and Suriname. Int Dent J. 2012;62(4):213-21. DOI:10.1111/j.1875-595X.2012.00116.x^,44 Carrera CA, Giacaman RA, Muñoz-Sandoval C, Cury JA. Total and soluble fluoride content in commercial dentifrices in Chile. Acta Odontol Scand. 2012;70(6):583-8. DOI:10.3109/00016357.2011.640287^,1111 Cury JA, Tabchoury CPM, Piovano S. Concentration and stability of fluoride in dentifrices market in Buenos Aires. Bol Asoc Argent Odontol Ninos. 2006;35(2):4-8.^,1717 Giacaman RA, Carrera CA, Muñoz-Sandoval C, Fernandez C, Cury JA. Fluoride content in toothpastes commercialized for children in Chile and discussion on professional recommendations of use. Int J Paediatr Dent. 2013;23(2):77-83. DOI:10.1111/j.1365-263X.2012.01226.x

18 Hashizume LN, Lima YBO, Kawaguchi Y, Cury JA. Fluoride availability and stability of Japanese dentifrices. J Oral Sci. 2003;45(4):193-9. DOI:10.2334/josnusd.45.193^-1919 Jordan RA, Markovich L, Gaengler P, Zimmer S. Total and free fluoride concentrations of African dentifrices marketed in West Africa.Oral Health Prev Dent. 2011;9(1):53-8. DOI:10.3290/j.ohpd.a21285 The American legislation is an exception,^hh US Food and Drug Administration. CFR - Code of Federal Regulations. Title 21: Food and drugs. Washington (DC); 2013 [cited 201 Apr 30]. Chapter I, Food and Drug Administration Department of Health and Human Services, Subchapter D, Drugs from human use (part 355): anticaries drugs products for over the counter human use. Available from: http://www.gpo.gov/fdsys/browse/collectionCfr.action?collectionCode=CFR&searchPath=Title+21%2FChapter+I&oldPath=Title+21&isCollapsed=true&selectedYearFrom=2013ºycord=710 because besides establishing the maximum total fluoride amount that can be added to a toothpaste, it also requires they have and maintain a minimum concentration of soluble fluoride in the formulation. On the other hand, both the Europeanⁱi European Union. Statutory Instruments. Consumer Protection: The Cosmetic Products (Safety) Regulations 2008: nº 1284. London: Stationery Office; 2008 [cited 2015 Apr 30]. Available from: http://www.legislation.gov.uk/uksi/2008/1284/pdfs/uksi_20081284_en.pdf and the Mercosur legislations,^jj MERCOSUL. MERCOSUL/GMC/RES nº 48/02. Regulamento técnico MERCOSUL sobre lista de substâncias que os produtos de higiene pessoal, cosméticos e perfumes não devem conter, exceto nas condições e com as restrições estabelecidas . Brasília (DF): Sistema de Informação do Comércio Exterior; 2002 [cited 2015 Apr 30]. Available from: http://www.sice.oas.org/trade/mrcsrs/resolutions/res4802p.asp similarly to Brazilian legislation, only establish the maximum amount of total fluorine that a toothpaste should contain (0.15%).

CONCLUSIONS

Considering that:

• A fluoride toothpaste should have a concentration of at least 1,000 ppm of soluble fluoride to have anticaries effect;

• In the Brazilian market, some toothpastes containing no more than 1,500 ppm total fluoride but less than 1,000 ppm of soluble fluoride, have been found;

• The current resolution only prioritizes the safety of fluoride toothpastes, in detrimental of their anticaries effect;

ANVISA's Regulation 79, from August 28, 2000, should be immediately revised or another legal alternative measure must be taken to ensure that none Brazilian citizen runs the risk of using a fluoride toothpaste that is ineffective against dental caries.

REFERENCES

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