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. 2020 Nov 6;61(Suppl 3):74–80. doi: 10.1111/j.1875-595X.2011.00053.x

Benefits of a silica-based fluoride toothpaste containing o-cymen-5-ol, zinc chloride and sodium fluoride

Craig S Newby 1,*, Joanna L Rowland 1, Richard JM Lynch 1, David J Bradshaw 1, Darren Whitworth 1, Mary Lynn Bosma 1
PMCID: PMC9374939  PMID: 21762159

Abstract

Fluoride toothpastes in conjunction with tooth brushing are used to clean teeth, control plaque build-up and for anti-caries benefits. Toothpastes are designed with attractive flavours and appearances to encourage regular prolonged use to maximise these benefits. The incorporation of additional ingredients into toothpaste is a convenient way to provide supplementary protection that fits into people’s everyday oral care routine. Such ingredients should not compromise the primary health benefits of toothpaste nor discourage its use. o-Cymen-5-ol and zinc chloride have been incorporated into a sodium fluoride (NaF)/silica toothpaste at 0.1%w/w and 0.6%w/w respectively to provide additional benefits. These include improved gingival health maintenance, in terms of the reduction of plaque, gingival index and bleeding, and an immediate and long lasting reduction in volatile sulfur compounds (VSCs) measured on breath. These benefits can be attributed to the antimicrobial and neutralisation actions of the toothpaste. The use of established fluoride models demonstrated no compromise in NaF bioavailability. The toothpaste was formulated without compromising product aesthetics. The combination of o-cymen-5-ol and zinc chloride in toothpaste gave superior maintenance of gingival health and reduction in malodour related VSCs without compromising the primary health benefits of the toothpaste or diminishing attributes preferred for the product’s use.

Key words: Caries, fluoride, malodour, toothpaste

INTRODUCTION

People use toothpaste in conjunction with tooth brushing not only to clean teeth and control the build up of plaque but to gain access to other oral health benefits such as anti-caries, gum health and malodour control. The mechanical functions of toothpaste used in conjunction with tooth brushing are to: clean teeth by removing stain; remove food debris; minimise build-up of plaque and leave the mouth feeling clean and fresh. Toothpastes often contain specific ingredients to confer additional oral health benefits. The use of fluoride as an anti-caries agent being the most wide spread. Brushing must be carried out regularly and correctly and for a sufficient length of time to be effective1., 2., 3., 4. whilst an attractive flavour and appearance encourages regular prolonged use1., 2., 5..

FLUORIDE TOOTHPASTE AND CARIES

Since their introduction to mass markets over 50 years ago, the effectiveness of fluoride toothpastes in reducing dental caries has been proven beyond doubt, with many combinations of fluoride salt and abrasive base tested in numerous caries clinical trials (CCTs)6., 7., 8., 9., 10.. Recently, a comprehensive Cochrane systematic review of fluoride toothpastes for children concluded that “Supported by more than half a century of research, the benefits of fluoride toothpastes are firmly established. Taken together, the trials are of relatively high quality, and provide clear evidence that fluoride toothpastes are efficacious in preventing caries”11.

Both Cochrane12 and other comprehensive reviews13 have concluded that 1,000 ppm fluoride is the minimum concentration that is proven to be effective against caries based on data from CCTs. Further, increases in the anti-caries effectiveness of toothpastes have been associated with increasing fluoride concentration, both up to14., 15., 16. and well beyond17., 18., 19. the usual upper concentration limits of 1,000–1,500 ppm.

The anti-caries action of fluoride results from its favourable effect on tooth remineralisation and demineralization20. It is generally accepted that fluoride ions promote the remineralisation of tooth enamel21., 22., increase apatite structural stability23 and reduce the rate of demineralisation22., 24.. Fluoride has also been reported to inhibit the ability of plaque bacteria to generate acids that result in demineralisation25. To be active against caries when delivered from a dentifrice, fluoride needs to be in a soluble bioavailable form so fluoride ions can be retained in reservoirs such as plaque26 and penetrate demineralised areas of the tooth enamel27., 28.. Factors such as pH29 and choice of formulation ingredients30., 31., 32., 33. have been demonstrated to have a marked effect on fluoride uptake in vitro and in vivo27., 34., 35.. There are several sources of fluoride currently utilised in marketed dentifrices: sodium fluoride (NaF); sodium monofluorophosphate (MFP); stannous fluoride (SnF2); and organic fluorides such as ‘amine fluoride’ (N’-octadecyltrimethylenediamine-N,N,N’- tris(2-ethanol)-dihydrofluoride). There is some controversy concerning the relative efficacy of each source, particularly between the two most widely studied sources, NaF and MFP36., 37.. On balance, the scientific literature seems to suggest that NaF dentifrices are slightly more effective than those employing MFP32., 38., 39., 40., 41., 42.. This is most likely because monofluorophosphate ions need to hydrolyse in the mouth to release free fluoride ions for efficacy43.

TOOTHPASTE AND GUM HEALTH

Plaque-induced gingivitis, in the absence of clinical attachment loss, is the most common form of periodontal disease, affecting 50–90% of the adult population44., 45.. Although the specific mechanisms underlying gingivitis requires further investigation, it is widely accepted that an excess accumulation of dental plaque and associated by-products at the gum margin produces gingivitis46. If left untreated, gingivitis can progress to periodontitis which may eventually lead to tooth loss. Recent findings also suggest that periodontal disease may be related to certain systemic conditions47. Whilst gingivitis may usually be prevented or treated by a diligent oral hygiene regime to facilitate the removal of dental plaque, many people fail to carry out meticulous oral hygiene, and thus the incorporation of additional antimicrobial actives in toothpastes as an adjunct to mechanical plaque control is a convenient way to provide additional protection against plaque and gingivitis that fits into people’s everyday oral care routines48., 49.. Such agents including triclosan, zinc salts and stannous are discussed in a review by Brading and Marsh50 and further by Pizzey et al.51.

TOOTHPASTE AND HALITOSIS

Bad breath, oral malodour and halitosis are interchangeable terms used to describe unpleasant smells that emanate from the mouth. Halitosis has been defined as an unpleasant odour that emanates from the oral cavity with intra-oral and or extra-oral origins52. Up to 50% of people worldwide assess themselves as having halitosis53 causing serious social and psychological concerns for sufferers. Whilst halitosis can originate from the stomach or lungs, it is thought that up to 90% of breath odour is intra-oral and emanates from the mouth54., 57.. A study by Tangerman and Winkel56 concluded that the volatile sulphur compounds (VSCs), methyl mercaptan and hydrogen sulfide were the prevalent odour causing compounds associated with intra oral halitosis, whilst dimethyl sulfide was the only compound found in significant levels associated with extra-oral halitosis. VSCs are produced in the mouth by the bacterial putrefaction of amino acids derived from food, cells, saliva and blood55., 57.. The most common bacteria associated with halitosis are gram negative anaerobes such as Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum58., 59., 60.. These bacteria can be harboured between teeth and in periodontal pockets associated with an oral disease state, however the posterior dorsal surface of the tongue is considered the primary source of intra-oral halitosis in healthy individuals57., 61., 62..

As with many oral conditions, mechanical removal of biofilms and micro-organisms is the first step in the control of halitosis. Whilst good oral hygiene and cleaning of the tongue help control halitosis (review by Armstrong et al.52), a Cochrane systematic review concluded that the use of scrapers to clean the tongue in addition to tooth brushing produced a reduction in VSCs, However this effect was small and was not long term63. Research shows that people recognise an improvement in social life upon satisfactory treatment for halitosis64.

Again, as many people fail to carry out meticulous oral hygiene, the incorporation of additional ingredients into toothpaste is a convenient way to provide additional help to control oral malodour that fits into people’s everyday oral care routine.

FORMULATION DEVELOPMENT

Toothpastes contain a number of ingredients that serve a definite purpose in providing the attributes required by the consumer in a modern product. Toothpastes should be designed to deliver fluoride efficacy, to be able to clean teeth effectively and to taste and feel good for use by the target consumer. Toothpastes that give additional benefits should be designed not to compromise the primary reasons for toothpaste use and additional ingredients need to be efficacious when delivered from toothpaste in ordinary use. Several key ingredients are further discussed.

The polishing or abrasive agent

The polishing or abrasive agent will help to eliminate stained pellicle and plaque from the teeth thus restoring the natural lustre and enamel whiteness. Without an abrasive, teeth can become stained65. The polishing or abrasive agent must be chosen carefully so that it can clean without damaging the enamel or the much softer underlying tissue, dentine. Consideration of the target user when choosing the polishing or abrasive agent is therefore required. Several abrasive systems including calcium carbonate, dicalcium phosphate dihydrate, alumina and silicas are currently found in commercial toothpastes as they are effectively insoluble, inert, nontoxic and preferably white. The use of calcium based abrasives should generally be avoided when used in conjunction with NaF to ensure available fluoride compatibility66.

The thickening system

A binder and thickening system controls the stability and consistency of toothpaste and affects the ease of dispersion of the paste in the mouth. Choice of the correct binder and concentration is critical to ensure that the product can be readily squeezed from the tube and yet have a good appearance when it is on the toothbrush.

The surfactant agent

The surfactant agent provides foam and aids dispersion of the product in the mouth. The detergent used most widely is sodium lauryl sulphate (SLS), which has a history of decades of safe and effective use all over the world. The safety of SLS has been reviewed by the USA based expert panel The Cosmetics Ingredient Review (CIR)67., 68., Organisation for Economic and Development (OECD)69 and National Industrial Chemicals Notification and Assessment Scheme (NICNAS)70. The CIR concluded in 1983 and later in 2005, that SLS as used in cosmetic products, including oral hygiene products, is safe for use in rinse off products designed for brief, discontinuous use. Following a human safety assessment on SLS, in 1997, the OECD concluded SLS was a low hazard to consumer safety. This was also verified by NICNAS in 2007. In addition SLS is also an ingredient which is not prohibited or restricted for use, under the European Cosmetics Directive71.

Another role SLS has, is to help to solubilise other key toothpaste ingredients such as flavours and certain antimicrobial agents.

The humectant

The humectant in a toothpaste helps to reduce the loss of moisture from the product. In toothpaste, the humectants minimise plug formation and improve the texture and feel of the product in the mouth. Examples are glycerine and sorbitol which are the humectants used most often.

The flavour

The choice of flavour is very important to the consumer. Flavours are often developed in combination with sweetening agents such as soluble saccharin to ensure the product is pleasant to use and should also leave a fresh taste in the mouth after use.

Toothpaste containing 0.1%o-cymen-5-ol and 0.6% zinc chloride

o-Cymen-5-ol and zinc chloride have been formulated into a NaF/silica toothpaste at 0.1%w/w and 0.6%w/w respectively to provide additional benefits without compromising the primary functions for toothpaste use.

Zinc salts are used in oral healthcare products to provide meaningful and clinically relevant therapeutic benefits to the consumer50., 51.. Zinc salts in toothpastes, including zinc chloride, have a long and safe history of safe use. Zinc is an essential mineral for many human biological functions. Potential zinc exposure following the intended use of the toothpaste as directed is less than the Recommended Daily Allowance (RDA) for zinc established by the U.S. Institute of Medicine, Food and Nutrition Board (8–11 mg zinc/day)72. It is important to note that the RDA is the average daily nutrient intake recommended simply to meet the nutritional requirements of nearly all (97–98%) healthy individuals in a particular life stage and gender group.

This concentration of zinc chloride at 0.6%w/w complies with approved regulatory limits. Zinc salts are approved for use in cosmetic products (including oral applications) marketed in the European Union with a concentration limit of 1.0% as elemental zinc73.

The inclusion of o-cymen-5-ol in this toothpaste does not present a safety concern when the product is used as directed. o-Cymen-5-ol (CAS# 3228-02-2), synonymous with 3-methyl-4-isopropylphenol or IPMP, is an isopropyl cresol used typically as a preservative. Extensive toxicological data on o-cymen-5-ol or its structural congeners exist in the published scientific literature to support its safety at low levels in toothpaste74. GSK have also conducted oral tolerance studies to support the safety of o-cymen-5-ol in toothpaste at a concentration of 0.1%w/w including those reported by Kakar75., 76. and Payne 77.

o-Cymen-5-ol has been reviewed by the expert scientific panel of the Cosmetic Ingredient Review in the US and classified as safe for use in cosmetics up to 0.5%w/w78. o-Cymen-5-ol is approved in Japan as a quasi-drug as an anti-inflammatory active and is listed within the Japanese oral care monograph up to a level of 0.1%w/w79. This ingredient has a history of safe use in this market, in mouthwash and toothpaste products. o-Cymen-5-ol also has a history of safe use in cosmetic products marketed in Europe. Under the EU Cosmetics Directive o-cymen-5-ol is approved for use as a preservative with a limit of 0.1%w/w80.

By careful selection of the products ingredients and using today’s flavour masking technology, a toothpaste containing both zinc chloride and o-cymen-5-ol was developed that gave excellent family aesthetics (BASES data on file). Such a product has the desired characteristics for regular twice daily use to confer additional benefits without compromising the primary functions for toothpaste use.

Toothpastes formulated with 0.1%w/w o-cymen-5-ol and 0.6%w/w zinc chloride have been clinically proven to provide additional maintenance of gingival health benefits in the areas of reduced plaque, gingival index and bleeding beyond those attained by brushing with a conventional NaF/silica toothpaste75., 76.. These toothpastes provide a convenient way to provide additional protection for 50–90% of the adult population that fits into people’s everyday oral care routines. The unique combination of zinc chloride and o-cymen-5-ol has resulted in a spectrum of antimicrobial activity greater than for each of the ingredients alone51. The toothpaste formulations were designed to deliver both zinc and o-cymen-5-ol81.

The toothpaste formulated with 0.1%w/w o-cymen-5-ol and 0.6%w/w zinc chloride was proven to provide an immediate and dramatic reduction in VSCs with an action that lasted, maintaining a significant overnight reduction77. This control of VSCs in this in vivo study can be attributed to the neutralisation activity of zinc chloride (reviewed by Burnett et al.82) combined with the antimicrobial activity of o-cymen-5-ol and zinc chloride51.

When seeking to establish the anti-caries efficacy of a totally new anti-caries system, for example a new fluoride salt or a non-fluoride agent, a caries clinical trial is desirable. However, the high cost and duration of such trials has led to the development of alternative, pre-clinical methods for the evaluation of fluoride efficacy where a relatively minor change is made to proven anti-caries system. These methods are generally described as ‘bioequivalence studies’. Bodies such as the Fédération Dentaire Internationale (FDI) and the American Dental Association (ADA) have published guidelines for the use of such bioequivalence models83., 84.. These include protocols to assess the ability of a fluoride dentifrice to deliver bioavailable fluoride and to promote the remineralisation and inhibit demineralisation of enamel.

Bioavailable fluoride studies were conducted throughout the development of the o-cymen-5-ol and zinc chloride toothpaste. Toothpastes containing 0.1%w/w o-cymen-5-ol and 0.6%w/w zinc chloride and NaF at concentrations of between 900 and 1,500 ppm F- were manufactured and the bioavailable fluoride determined by water extraction ion chromatography as described by Newby et al.34. The analytical method has been validated to produce results in line with those referenced in the USA FDA anti-caries monograph28. The bioavailable fluoride analysed throughout ICH stability storage conditions always gave results greater than those outlined in the USA FDA anti-caries monograph28. The levels of fluoride were chosen to encompass those permitted for cosmetic and over the counter medicine fluoride toothpastes throughout the world.

The remineralisation and demineralisation model reported by Featherstone85 is one widely used to distinguish the remineralisation and demineralisation equivalence of toothpastes86., 87.. Toothpastes containing 0.1%w/w o-cymen-5-ol and 0.6%w/w zinc chloride and 1,450 ppm NaF were demonstrated to be equivalent in this model88. In addition a protection of demineralisation model based on that reported by Laucello et al.89 showed a preferential effect for the o-cymen-5-ol and zinc chloride toothpaste88. Zinc has long been reported to have a positive effect against enamel demineralisation90 whilst more recently zinc has been recently reported to have a positive, fluoride related remineralisation benefits when used in conjunction with fluoride91., 92..

SUMMARY AND CONCLUSION

Toothpastes that give additional benefits beyond the primary reasons for use, such as clean teeth, plaque control and fluoride delivery for anti-caries activity should be designed not to compromise these benefits. The incorporation of o-cymen-5-ol and zinc chloride into toothpaste has yielded the additional product benefits of improved maintenance of gingival health benefits and long term control of VSCs. Both ingredients were formulated without compromising the in-use taste or aesthetics, the abrasion and cleaning characteristics of a silica based family toothpaste and without reducing the available ionic fluoride sourced from sodium fluoride. Both ingredients are safe for family use in toothpaste when used as directed. o-Cymen-5-ol and zinc chloride can be incorporated into toothpaste to give addition benefits beyond that of standard toothpaste without compromising the benefits of a standard toothpaste.

CONFLICT OF INTEREST AND SOURCE OF FUNDING

The work described in this manuscript was funded by GlaxoSmithKline Consumer Healthcare. The authors are employed by GSK but confirm no potential conflicts of interest.

REFERENCES

  • 1.Pader M. Marcel Dekker; New York: 1988. Oral hygiene products and practice; pp. 141–194. [Google Scholar]
  • 2.Zero DT, Creeth JE, Bosma ML, et al. The effect of brushing time and dentifrice quantity on fluoride delivery in vivo and enamel surface microhardness in situ. Caries Res. 2010;44:90–100. doi: 10.1159/000284399. [DOI] [PubMed] [Google Scholar]
  • 3.Ashley FP, Attrill DC, Ellwood RP, et al. Toothbrushing habits and caries experience. Caries Res. 1999;33:401–402. doi: 10.1159/000016540. [DOI] [PubMed] [Google Scholar]
  • 4.Chesters RK, Huntington E, Burchell CK, Stephen KW. Effect of Oral Care Habits on Caries in Adolescents. Caries Res. 1992;26:299–304. doi: 10.1159/000261456. [DOI] [PubMed] [Google Scholar]
  • 5.Dudding NJ, Dahl LO, Muhler JC. Patient reaction to brushing teeth with water, dentifrice or salt and soda. J Periodontol. 1961;31:386–392. [Google Scholar]
  • 6.Mainwaring PJ, Naylor MN. A four-year clinical study to determine the caries-inhibiting effect of calcium glycerophosphate and sodium fluoride in calcium carbonate base dentifrices containing sodium monofluorophosphate. Caries Res. 1983;17:267–276. doi: 10.1159/000260677. [DOI] [PubMed] [Google Scholar]
  • 7.Muhler JC, Radike AW, Nebergall WH, Day HG. Effect of a stannous fluoride-containing dentifrice on caries reduction in children. II. Caries experience after one year. J Am Dent Assoc. 1955;50:163–166. doi: 10.14219/jada.archive.1955.0028. [DOI] [PubMed] [Google Scholar]
  • 8.Mitropoulos CM, Holloway PJ, Davies TG, et al. Relative efficacy of dentifrices containing 250 or 1000 ppm F- in preventing dental caries--report of a 32-month clinical trial. Community Dent Health. 1984;1:193–200. [PubMed] [Google Scholar]
  • 9.Koch G, Bergmann-Arnadottir I, Bjarnason S, et al. Caries-preventive effect of fluoride dentifrices with and without anticalculus agents: a 3-year controlled clinical trial. Caries Res. 1990;24:72–79. doi: 10.1159/000261242. [DOI] [PubMed] [Google Scholar]
  • 10.Stephen KW, Chestnutt IG, Jacobson AP, et al. The effect of NaF and SMFP toothpastes on three-year caries increments in adolescents. Caries Res. 1994;28:277–283. [PubMed] [Google Scholar]
  • 11.Marinho VCC, Higgins JPT, Logan S et al. Fluoride toothpastes for preventing dental caries in children and adolescents. Cochrane Database Syst Rev 2003, Issue 1. Art No. CD002278. DOI: 10.1002/14651858.CD002278. [DOI] [PMC free article] [PubMed]
  • 12.Walsh T, Worthington HV, Glenny AM et al. Fluoride toothpastes of different concentrations for preventing dental caries in children and adolescents. Cochrane Database Syst Rev. 2010, Issue 1. Art No.: CD007868. DOI: 10.1002/14651858. CD007868.pub2. [DOI] [PubMed]
  • 13.Wong MCM, Clarkson J, Glenny AM, et al. Cochrane Reviews on the Benefits/Risks of Fluoride Toothpastes. J Dent Res. 2011;90:573–579. doi: 10.1177/0022034510393346. [DOI] [PubMed] [Google Scholar]
  • 14.Conti AJ, Lotzkar S, Daley R, et al. A 3-year clinical trial to compare efficacy of dentifrices containing 1.14% and 0.76% sodium monofluorophosphate. Community Dent Oral Epidemiol. 1988;16:135–138. doi: 10.1111/j.1600-0528.1988.tb00560.x. [DOI] [PubMed] [Google Scholar]
  • 15.Reed MW. Clinical evaluation of three concentrations of sodium fluoride in dentifrices. J Am Dent Assoc. 1973;87:1401–1403. doi: 10.14219/jada.archive.1973.0618. [DOI] [PubMed] [Google Scholar]
  • 16.Lu KH, Yen DJ, Zacherl WA, et al. The effect of a fluoride dentifrice containing an anticalculus agent on dental caries in children. ASDC J Dent Child. 1985;52:449–451. [PubMed] [Google Scholar]
  • 17.Stephen KW, Creanor SL, Russell JI, et al. A 3-year oral health dose-response study of sodium monofluorophosphate dentifrices with and without zinc citrate: anti-caries results. Community Dent Oral Epidemiol. 1988;16:321–325. doi: 10.1111/j.1600-0528.1988.tb00574.x. [DOI] [PubMed] [Google Scholar]
  • 18.Nordström A, Birkhed D. Preventive effect of high-fluoride dentifrice (5,000 ppm) in caries-active adolescents: a 2-year clinical trial. Caries Res. 2010;44:323–331. doi: 10.1159/000317490. [DOI] [PubMed] [Google Scholar]
  • 19.Biesbrock AR, Gerlach RW, Bollmer BW, et al. Relative anti-caries efficacy of 1100, 1700, 2200, and 2800 ppm fluoride ion in a sodium fluoride dentifrice over 1 year. Community Dent Oral Epidemiol. 2001;29:382–389. doi: 10.1034/j.1600-0528.2001.290508.x. [DOI] [PubMed] [Google Scholar]
  • 20.White DJ. Reactivity of fluoride dentifrices with artificial caries III. Quantitative aspects of acquired acid resistance: F uptake, retention, surface hardening and demineralisation. J Clin Dent. 1991;3:6–14. [PubMed] [Google Scholar]
  • 21.Silverstove LM. In: Clinical uses of fluorides. Wei SHY, editor. Lea and Febiger; Philadelphia: 1985. Fluorides and remineralisation; pp. 153–175. [Google Scholar]
  • 22.Featherstone JDB, Glena R, Shariati M, et al. Dependence of in vitro demineralisation of apatite and remineralisation of dental enamel on fluoride concentration. J Dent Res. 1990;69:620–625. doi: 10.1177/00220345900690S121. [DOI] [PubMed] [Google Scholar]
  • 23.Aoba T. The effect of fluoride on apatite structures and growth. Crit Rev Oral Biol Med. 1997;8:136–153. doi: 10.1177/10454411970080020301. [DOI] [PubMed] [Google Scholar]
  • 24.Chow LC. Tooth-bound fluoride and dental caries. J Dent Res. 1990;69:595–600. doi: 10.1177/00220345900690S117. [DOI] [PubMed] [Google Scholar]
  • 25.Marquis RE, Clock SA, Mota-Meira M. Fluoride and organic weak acids as modulators of microbial physiology. FEMS Microbiol Rev. 2003;26:493–510. doi: 10.1111/j.1574-6976.2003.tb00627.x. [DOI] [PubMed] [Google Scholar]
  • 26.Zero DT, Raubertas RF, Pedersen AM, et al. Studies of fluoride retention by oral soft tissues after the application of home-use topical fluorides. J Dent Res. 1992;71:1546–1552. doi: 10.1177/00220345920710090101. [DOI] [PubMed] [Google Scholar]
  • 27.Stookey GK. In: Clinical uses of fluorides. Wei SHY, editor. Lea and Febiger; Philadelphia: 1985. Are all fluoride dentifrices the same? pp. 105–131. [Google Scholar]
  • 28.Anti-caries drug products use for the over-the-counter human use; Final Monograph. Federal Register 60 No. 1984, 52474-52510, 1995
  • 29.Friberfer P. The effect of pH upon fluoride uptake in intact enamel. Scand J Dent Res. 1975;83:339–344. doi: 10.1111/j.1600-0722.1975.tb00447.x. [DOI] [PubMed] [Google Scholar]
  • 30.White DJ, Faller RV. Fluoride uptake from an anti-calculus NaF Dentifrice in vitro. Caries Res. 1986;20:332–336. doi: 10.1159/000260953. [DOI] [PubMed] [Google Scholar]
  • 31.Melsen B, Rølla G. Reduced clinical effect of monofluorophosphate in the presence of lauryl sulphate. Caries Res. 1983;17:549–553. doi: 10.1159/000260716. [DOI] [PubMed] [Google Scholar]
  • 32.Schemehorn BR, Wood DG, Winston AE. Laboratory Enamel Solubility Reduction and fluoride Uptake from Enamelon Dentifrice. J Clin Dent. 1999;10:9–12. [PubMed] [Google Scholar]
  • 33.Regatati B, Hotz P. Effect of pyrophosphate and diphosphonate on fluoride uptake by hydroxyapatite. Helv Odont Acta. 1970;14:42–44. [PubMed] [Google Scholar]
  • 34.Newby CS, Creeth JE, Rees GD, et al. Surface Microhardness Changes, Enamel Fluoride Uptake and Fluoride Availability from Commercial Toothpastes. J Clin Dent. 2006;17:94–99. [PubMed] [Google Scholar]
  • 35.Stamm JW. In: Relative efficacy of Sodium Fluoride and sodium monofluorophosphate dentifrices as anti-caries agent in dentifrices. Bowwn WH, editor. Royal Society of Medicine Press Limited; London: 1984. Clinical studies of neutral sodium fluoride and sodium monofluorophosphate dentifrices; pp. 105–131. [Google Scholar]
  • 36.Volpe AR, Petrone ME, Davies RM. A critical review of the 10 pivotal caries clinical studies used in a recent meta-analysis comparing the anti-caries efficacy of sodium fluoride and sodium monofluorophosphate dentifrices. Am J Dent. 1993;6:13–42. [PubMed] [Google Scholar]
  • 37.Sullivan RJ, Fletcher R, Bachiman R, et al. Intra-oral comparison and evaluation of the ability of fluoride dentifrices to promote the remineralisation of caries-like lesions in dentine and enamel. J Clin Dent. 1995;6:135–138. [PubMed] [Google Scholar]
  • 38.DePaola PF, Soparkar PM, Triol C, et al. The relative anti-caries effectiveness of sodium monofluorophosphate and sodium fluoride as contained in currently available dentifrice formulations. Am J Dent. 1993;6:7–12. [PubMed] [Google Scholar]
  • 39.Johnson MF. Comparative efficacy of NaF and SMFP dentifrices in caries prevention: A meta-analytic overview. Caries Res. 1993;27:328–336. doi: 10.1159/000261562. [DOI] [PubMed] [Google Scholar]
  • 40.Marks RG, Conti AJ, Moorhead JE, Cancro L, D’Agostino RB. Results from a three-year caries clinical trial comparing NaF and SMFP fluoride formulations. Int Dent J. 1994;44(3 Suppl 1):275–285. [PubMed] [Google Scholar]
  • 41.Stephen KW, Chestnutt IG, Jacobson AP, et al. The effect of NaF and SMFP toothpastes on three-year caries increments in adolescents. Int Dent J. 1994;44:287–295. [PubMed] [Google Scholar]
  • 42.Proskin HM, Volpe AR. Comparison of the anti-caries efficacy of dentifrices containing fluoride or sodium monofluorophosphate. Am J Dent. 1995;8:51–58. [PubMed] [Google Scholar]
  • 43.Bowen WH. The role of fluoride toothpastes in the prevention of dental caries. J R Soc Med. 1995;88:505–507. [PMC free article] [PubMed] [Google Scholar]
  • 44.American Academy of Periodontology Parameter on plaque-induced gingivitis. J Periodontol. 2000;71:851–852. doi: 10.1902/jop.2000.71.5-S.851. [DOI] [PubMed] [Google Scholar]
  • 45.NICE. Dental recall interval between routine dental examinations. Clinical guideline 19. October 2004.
  • 46.Löe H, Theilade E, Jensen SB. Experimental gingivitis in man. J Periodontol. 1965;36:177–187. doi: 10.1902/jop.1965.36.3.177. [DOI] [PubMed] [Google Scholar]
  • 47.Williams RC, Barnett AH, Claffey N, et al. The potential impact of periodontal disease on general health: a consensus view. Current Med Res Opinion. 2008;24:1635–1643. doi: 10.1185/03007990802131215. [DOI] [PubMed] [Google Scholar]
  • 48.Hull PS. Chemical inhibition of plaque. J Clin Periodontol. 1980;7:431–442. doi: 10.1111/j.1600-051x.1980.tb02150.x. [DOI] [PubMed] [Google Scholar]
  • 49.Kornman KS. The role of supragingival plaque in the prevention and treatment of periodontal diseases. A review of current concepts. J Periodont Res. 1986;21(Suppl 16):5–22. [Google Scholar]
  • 50.Brading MG, Marsh PD. The oral environment: the challenge for antimicrobials in oral care products. Int Dent J. 2003;53:353–362. doi: 10.1111/j.1875-595x.2003.tb00910.x. [DOI] [PubMed] [Google Scholar]
  • 51.Pizzey R, Bradshaw DJ, Marquis R. Antimicrobial Effects of o-Cymen-5-ol and Zinc, Alone & In Combination in Simple Solutions and Toothpaste Formulations. Int Dent J. 2011;61:33–40. doi: 10.1111/j.1875-595X.2011.00047.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Armstrong BL, Sensat ML, Stoltenberg JL. Halitosis: A review of current literature. J Dental Hygiene. 2010;84:65–74. [PubMed] [Google Scholar]
  • 53.Porter SR, Scully C. Oral malodour (halitosis) Br Med J. 2006;333:632–635. doi: 10.1136/bmj.38954.631968.AE. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Delanghe G, Ghyselen J, Bollen C, et al. An inventory of patients’ response to treatment at a multidisciplinary breath odor clinic. Quintessence Int. 1999;30:307–310. [PubMed] [Google Scholar]
  • 55.ADA council on scientific affairs Oral malodour. J Am Dent Assoc. 2003;134:209–214. [Google Scholar]
  • 56.Tangerman A, Winkel EG. Intra- and extra-oral halitosis: Findings of a new form of extra-oral blood-borne halitosis caused by dimethyl sulphide. J Clin Periodontol. 2007;34:718–755. doi: 10.1111/j.1600-051X.2007.01116.x. [DOI] [PubMed] [Google Scholar]
  • 57.Scully C, Felix DH. Oral medicine – update for the dental practitioner. Oral malodour. Br Dent J. 2005;199:498–500. doi: 10.1038/sj.bdj.4812806. [DOI] [PubMed] [Google Scholar]
  • 58.De Boever EH, De Uzeda M, Loesche WJ. Relationship between volatile sulfur compounds, BANA-hydrolyzing bacteria and gingival health in patients with and without complaints of oral malodor. J Clin Dent. 1994;4:114–119. [PubMed] [Google Scholar]
  • 59.Koshimune S, Awano S, Gohara K, et al. Low salivary flow and volatile sulfur compounds in mouth air. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;96:38–41. doi: 10.1016/s1079-2104(03)00162-8. [DOI] [PubMed] [Google Scholar]
  • 60.Spratt DA, Pratten J. Biofilms and the oral cavity. Revs in Environmental Science Biotechnol. 2003;2:109–120. [Google Scholar]
  • 61.Lee CH, Kho HS, Chung SC, et al. The relationship between volatile sulfur compounds and major halitosis-inducing factors. J Periodontol. 2003;74:32–37. doi: 10.1902/jop.2003.74.1.32. [DOI] [PubMed] [Google Scholar]
  • 62.Sanz M, Roldan S, Herrera D. Fundamentals of breath malodour. J Contemp Dent Pract. 2001;2:1–17. [PubMed] [Google Scholar]
  • 63.Outhouse TL, Fedorowicz Z, Keenan JV, et al. A Cochrane systemic review finds tongue scrapers have short-terms efficacy in controlling halitosis. Gen Dent. 2006;54:325–359. 360, 367-368. [PubMed] [Google Scholar]
  • 64.Kishi M, Abe A, Yonemitsu M. Relationship between the SF-36 questionnaire and patient’s satisfaction following halitosis therapy. Oral Dis. 2005;11(supply 1):89–91. doi: 10.1111/j.1601-0825.2005.01102.x. [DOI] [PubMed] [Google Scholar]
  • 65.Davis WB. Cleaning and polishing of teeth by brushing. Community Dent Oral Epidemiol. 1980;8:237–243. doi: 10.1111/j.1600-0528.1980.tb01295.x. [DOI] [PubMed] [Google Scholar]
  • 66.Bibby B. Test of the effect of fluoride-containing dentifrices on dental caries. J Dent Res. 1945;24:297–303. doi: 10.1177/00220345450240060301. [DOI] [PubMed] [Google Scholar]
  • 67.Cosmetic Ingredient Review: Final report on the safety assessment of sodium lauryl sulphate and ammonium lauryl sulfate. Journal of the American College of Toxicology. 1983;2:127–181. [Google Scholar]
  • 68.Cosmetic Ingredient Review: Final report on the safety assessment of sodium lauryl sulphate and ammonium lauryl sulfate. Int J Toxicol. 2005;24:1–10. [Google Scholar]
  • 69.OECD Screening Information Data Set (SIDS) OECD; Paris: 1997. Initial Assessment Report Volume 4, Part 2: Sodium Dodecyl Sulfate. [Google Scholar]
  • 70.NICNAS Existing Chemical Information Sheet . NICAS; Australia: 2007. Sodium Lauryl Sulphate CAS No: 151-21-3. 09 Oct. [Google Scholar]
  • 71.EU Cosmetics directive 76/768/EEC Annex II List of Substances which must not form part of the Composition of Cosmetic Products. Annex III List of Substances which Cosmetic Products must not contain except subject to the restrictions and conditions laid down
  • 72.Institute of Medicine, Food and Nutrition Board . National Academy Press; Washington, DC: 2001. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. http:ods.od.nih.govfactsheetsZinc. [PubMed] [Google Scholar]
  • 73.EU Cosmetics directive 76/768/EEC, Annex III/23, Water-soluble zinc salts with the exception of zinc 4-hydroxy-benzenesulphonate and zinc pyrithione 1% calculated as zinc
  • 74.Cosmetic Ingredient Review (CIR) Expert Panel Final Report on the Safety Assessment of Sodium p-Chloro-m-Cresol, p-Chloro-m-Cresol, Chlorothymol, Mixed Cresols, m-Cresol, o-Cresol, p-Cresol, Isopropyl Cresols, Thymol, o-Cymen-5-ol, and Carvacrol. Int J Toxicology. 2006;25:29–127. doi: 10.1080/10915810600716653. [DOI] [PubMed] [Google Scholar]
  • 75.Kakar A, Newby EE, Kakar K, et al. A randomised clinical trial to assess maintenance of gingival health by a novel dentifrice containing 0.1%w/w o-cymen-5-ol and 0.6%w/w zinc chloride. Int Dent J. 2011;61:13–20. doi: 10.1111/j.1875-595X.2011.00044.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76.Kakar A, Newby EE, Ghosh S, et al. A randomised clinical trial to assess maintenance of gingival health by a novel gel to foam dentifrice containing 0.1%w/w o-cymen-5-ol, 0.6%w/w zinc chloride. Int Dent J. 2011;61:21–27. doi: 10.1111/j.1875-595X.2011.00045.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 77.Payne D, Gordon J, Nisbet S, et al. A randomised clinical trial to assess control of oral malodour by a novel dentifrice containing 0.1%w/w o-cymen-5-ol and 0.6%w/w zinc chloride. Int Dent J. 2011;61:60–66. doi: 10.1111/j.1875-595X.2011.00051.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 78.http://www.cosmeticsinfo.org/ingredient_details.php?ingredient_id=95
  • 79.Japanese Standards of Quasi-drug Ingredients 2006 (JSQI)
  • 80.EU Cosmetics directive 76/768/EEC, Annex VI/38, 4-Isopropyl-m-cresol
  • 81.Yang J, Deol G, Myanger N. Retention of o-cymen-5-ol and zinc on reconstructed human gingival tissue from a toothpaste formulation. Int Dent J. 2011;61:41–45. doi: 10.1111/j.1875-595X.2011.00048.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 82.Burnett GR, Stephen AS, Pizzey R, et al. In vitro effects of novel toothpaste actives on components of oral malodour. Int Dent J. 2011;61:67–73. doi: 10.1111/j.1875-595X.2011.00052.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 83.Guidelines for the acceptance of fluoride-containing dentifrices. J Am Dent Assoc. 1985;110:545–547. doi: 10.14219/jada.archive.1985.0366. [DOI] [PubMed] [Google Scholar]
  • 84.Guidance on the assessment of the efficacy of toothpastes. Int Dent J. 1999;49:311–316. doi: 10.1111/j.1875-595x.1999.tb00530.x. [DOI] [PubMed] [Google Scholar]
  • 85.Featherstone JDB, O’Reilly MM, Shariati M, et al. In: Factors Relating to Demineralisation and Remineralisation of the Teeth. Leach SA, editor. IRL Press Ltd; Oxford: 1986. Enhancement of remineralisation in vitro and in vivo; pp. 23–34. [Google Scholar]
  • 86.Pfarrer AM, McQueen CM, Lawless MA, et al. Anticaries potential of a stabilized stannous fluoride/sodium hexametaphosphate dentifrice. Compendium. 2005;26(9 Suppl 1):41–46. [PubMed] [Google Scholar]
  • 87.Toda S, Featherstone JD. Effects of fluoride dentifrices on enamel lesion formation. J Dent Res. 2008;87:224–227. doi: 10.1177/154405910808700303. [DOI] [PubMed] [Google Scholar]
  • 88.Churchley D, Newby CS, Lynch RJM, et al. Protection against enamel demineralisation using toothpaste containing o-cymen-5-ol, zinc chloride and sodium fluoride. Int Dent J. 2011;61:55–59. doi: 10.1111/j.1875-595X.2011.00050.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89.Laucello M, Noel N, Ferro R, et al. The anti-caries efficacy of a silica-based fluoride toothpaste containing zinc citrate, triclosan, vitamin E and sunflower oil. Int Dent J. 1999;49:311–316. [Google Scholar]
  • 90.Brudevold F, Steadman LT, Spinelli MA, et al. A study of zinc in human teeth. Arch Oral Biol. 1963;8:135–144. doi: 10.1016/0003-9969(63)90051-7. [DOI] [PubMed] [Google Scholar]
  • 91.Lynch RJM, Churchley DD, Butler A, et al. Effects of zinc and fluoride on the remineralisation of artificial carious lesions under simulated plaque-fluid conditions. Caries Res. 2011;45:313–322. doi: 10.1159/000324804. [DOI] [PubMed] [Google Scholar]
  • 92.Lynch RJM. Zinc in the mouth, its interactions with dental enamel and possible effects on caries; a review of the literature. Int Dent J. 2011;61:46–54. doi: 10.1111/j.1875-595X.2011.00049.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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