The decline in dental caries revalence and incidence in the last two decades is eonsidered to be largely~to ..th~wead use of fluoride. owever, the prevalence of dental fluorosis has increased

simultane slv, The inerease is in the mild and very mild forms of fluorosis, both in fluoridated and in non-'"fluoridated areas. A large arnount of epidemiologieal data demonstrates that the occurrenee of dental fluorosisis associated with exeessive fluoride intake throughout the period oftooth development. Multiple sources offluoride intake have been identified. This review deseribes the condition and summarizes the recent literatureon the risk faetors for dental fluorosis. Four major risk faetors have been eonsistently identified: use offluoridated drinking water, fluoride supplements, fluoride dentifrice and infant formulas. In addition, somemanufaetured ehildren foods and drinks may also be important contributors to total daily fluoride intake.

UNITERMS: Fluoride; Dental fluorosis, risk.

INTRODUCTION

J:here has been a decline in dental cariesprevalence and incidence durin the last twodecades both in economicali develo d36,60,61,69andin economicaliy developing countries37,67,107.This

Jige~se is considered to be largely due tolhe~.§pr:ead use of fluoride. Concurrent with the

~ decline in caries, an increase in the revalence ofdental fluorosis has been documented, inêommunities with43,55,101,103and without fluoridatedarrnking water43,55.80.101.Concem with the increasein the prevalence of fluorosis has led to many studieson the reasons for the increase, and in identifyingthe important risk factors. These studies have haddifferent designs and employed differentpopulations, many with multiple sources offluorideexposure. Further, they have used different indicesto diagnose and score dental fluorosis. This hasmade it difficult to compare the results of thesestudies. The purpose of this review is to summarize

p<"4~f~ f LJ\-DPJ:6u

the recent literature on risk factors for dentalfluorosis.r Dental fluorosis is a fluoride- induced disturbancein tooth formation, which results in hypomineralized

, enamel with increased porosity". It is caused byI excessive fluoride intake but only during the period

I

of tooth development'v'v'<". The most importantrisk factor for fluorosis is the total amount of fluorideconsumed from ali sources during the critical periodof tooth development' 5.17,31.63.

The clinical appearance of mild dental fluorosisis characterized by bilateral, diffuse (not sharplydemarcated) opaque, white striations that runhorizontally across the enamel. These may beinvisible to the individual and the clinician but oftencan be seen after the enamel has been dried. Theopacities may coalesce to form white patches. Inthe more severe forms the enamel may becomediscolored andlor pitted24,26,97,98.Upon eruption intothe mouth, fluorosed enamel is not discolored - thestains develop over time due to the diffusion of

BUZALAF, M. A. R.; CURY, J.A.; WHITFORD, G.M.FLUORIDEEXPOSURESANDDENTALFLUOROSIS:AUTERATUREREVIEW

___ o

exogenous ions (eg, iron and copper) into theabnormally porous enameL

~e~ underlyin the de elQ me..!!!.Q[dental fluorosis lias not been conc1u~ely~as believed previously thatéxCesslve fliíoride intake interfered with the functionof ameloblasts, perhaps inhibiting the secretion of,or altering the composition of enamel matrixproteins. lt now appears that this is unlikely forseveral reasons inc1uding the fact that the risk ofdental fluorosis is lowest during the secretory stageof enamel development 16,17,27,28.

Microscopically, the structural arrangement ofthe crystals appears normal, but the width of theintercrystalline spaces is increásed,@!ng po~The degree and extent of porosity depends on theconcentration of fluoride in the tissue fluids duringtooth development25.I02 ln fac, e risk of dentalfluorosis base on animal shidies, is directl~

~

'-<o the interaction o clrculatlllg fIuoru ecoíiêêiitrations and time, fe:'- the area under the time-concentration curve Thus it appeãrs that dentalfluorosis can result from a range of plasma fluorideconcentrations provided that they are maintained forsufficientl y long periods 111.With increasing severityof fluorosis, the fluoride concentration throughoutthe enamel, the depth of enamel involvement, andthe degree of porosity also íncreases"-". Clinicalstudies of dental fluorosis have demonstrated that/"\...---- - --- -.--- -the most critical period for efevelopment of fluomsísís during thê õSf-secr:eto"ry or early maturati2!!-phase of tooth development 2;26-;52;7~:S4,J(J~

; Fluorosis islesãprêvalent and le;-apparent inprirnary teeth than in permanent teeth, and, in anycase, fluorosis of the prirnary teeth has only short-term rather than long-term consequences. Therefore,the major concern about fluorosis is with thepermanent teeth. Since the different permanent teeth~ atmfferent~~'period~.e den@~ ex.!.~ndsfrol!1eleven mc:nthsto seven years of ag~ The permanent maxillary---- ----- --- ..- .._-central incisors are of greatest cosmetic importanceánd they appear most at risk of fluorosis betweenages of fifteen and twenty-four months for males"ãiíQ-oetween fwenty-oiiê"ãiid thiity moº~s fm-,females23. Howéver:ãmeta-analysis of the riskperiods ássociated with the development of dentalfluorosis in maxillary permanent central incisorsshowed that the duration of excessi ve fluorideexposure throughout amelogenesis, rather thanspecific risk periods, would seem to explain thedevelopment of dental fluorosis".

Some authors regard to 0.1 mg Flkg body weight

per day as the exposure level above which dentalfluorosis occurs", although studies in Kenya havefound fluorosis with a daily fluoride intake of lessthan 0.03 mg Flkg body weight per day fromwater-". In these latter studies, however, the teethwere dried in order to detect the mildest forms offluorosis. A daily fluoride intake between 0.05 and0.07 mg/kg "ooây-weiglit -peidãy is generall yregarded as optimum for prevention of dentalcaries?". Other factors that may increase theSusceptibility of indi viduals to dental fluorosis arealtitudel.42,57.59.93,1I0,111,114,renal insufficiency45,46,82,104,SeM d '.!~I,..and malnutrition?':'!". Some of these~, .-however, can produce enamel changes tha~~~bledental fluorosis in the absence of signíficantexposure to fluoride. ~

Studies of dental fluorosis, done in areas Wi~and without fluoridated drinking water, haveidentified four major risk factors: use of fluoridateddrinking water, fluoride supplements, fluoridedentifrice, and infant formulas before the age ofseven years. Some manufactured children foods anddrinks may also be important contributors to totaldaily fluoride intake.

Fluoridated drinking water

Dean 14,in 1942, stated that some 10% of childrenin optimally fluoridated (1.0 ppm) areas wereaffected by mild or very mild fluorosis in thepermanent teeth and that less than 1% were soaffected in low-fluoride areas. These degrees of ri A~n Sprevalence were recorded p@~ the availabilityof fluoridated dental products when fluoridateddrinking water was the only significant source offluoride intake-". In North America, the prevalenceof dental fluorosis now ranges between 7.7% to 69%in fluoridated communities, and from 2.9% to 42%in non-fluoridated communities. The studies doneafter the 1980s have shown the highest prevalences'".The studies by Spuznar; Burt'? and Riordan" are inagreement that the risk of fluorosis in areas wherethe water fluoride concentration is 0.8 ppm is fourtimes higher than in non-fluoridatedcommunities'T'=". However, water fluorideprobably has its greatest impact on fluorosisprevalence indirectly, through being used in theprocessing of infant formulas, other children' s foodsand soft drinks". ln a systematic review of 214studies on water fluoridation, McDonagh et al.?'observed an increase in the proportion of caries-free children and a reduction in the number of teethaffected by caries. They also noted a dose-dependent

Rev.FOBV.9, n.1/2, p.1-10,jan./jun. 2001

increase in dental fluorosis. At a fluoride level of 1ppmin the drinking water, they estimated that 12.5%of exposed people would have fluorosis that theywould find of esthetic concem, a prevalence muchhigher than that reported by Dean 14in 1942 whofound virtually no cases of moderate or severefluorosis. The present-day prevalence of fluorosisindicates ~~g c~~tíng:f:1ÍÍÔfidefromsources in aaartíOi1to tha~Lllg.;----- - ----------waer.

" . Dietary fluoride supplements

Fluoride supplements are recommended forchildren living in fluoride deficient areas. Therecommended dai1y dose is based on the age of thechild and on the fluoride concentration in thedrinking water. However, there are many reportsshowing that supplements are prescribedinappropriately to children in fluoridatedareasS1,7S,100.Many studies have identified fluoridesupplements as risk factors for dental fluorosis, bothin fluoridated+":" and non-fluoridated areas40,43,49.

"'< Sl,74,7S.IOS.In fluoridated areas the risk of dental~ fluorosis from use of fluoride supplements is almost

~ 4 times higher than in non- flu2.ti.da~ed af_t:.as63,S7.~ ~e, the risk of dental fluorosis from the use of

fluoride supplements is well established. Cliniciansmust be sure of the water fluoride concentrations,

âSWell as of the caries risk of the child, beforepreSciibing fluori e supplements. The U.S. Centers1OfOlsease . onlíOl an revention has recentlyQublished uidelines for the judicious rescription?f dietary fluoride su lements 11.

Infant Formulas

Because of its very low fluoride contcentration,human breast milk is a poor source of fluoride. Ininfancy the major source of fluoride is consideredto be infant formulas. A number of studies haveimplicated the consumption of infant formulas as arisk factor for dental fluorosis, particularly influoridated areaslO.44·S3.71,SS,94,10S,but not in non-fluoridated áreas". Soy-based formulas have beenreported to have-sDmewhat high~:t:l.!liiíide_

êóncenfrations than milk-based formulas 10,94.1OSand'this has been attribí.ife~~er end~~~lsÕf1-1iíõfidem the soy extract44·54.65.However, themost important factor when considering infant'formUlãS-as risk'factors for dental fluorosis isthewater used to reconstitute them. When infantformulas are recorisfitutedwith optimally

fluoridated water, they provide a daily fluorideintake above that likely to cause some degree ofdental fluorosis'<". Therefore, to reduce the risk offluorosis the recommendation is to use ready-to-feed formulas whose fluoride concentrations areknown to be low, or low-fluoride bottled water to/>«: _

dilute the formula concentrate.-- ~~--Fluoride dentifrice

Ripa" reviewed studies that investigated thepossible association between the use of fluoridedentifrice and prevalence of dental fluorosis. Heconcluded that of the ten studies reviewed,nine7.9.18.39,49.74,96.99,113failed to find an association.These studies, however, were not designed withfluoride dentifrice effects as the major focus 01'usedsurrogate measures to evaluate fluoride dentifri[;~exposure.From this group of studies, the only on\iVused case control methodologles to assess t erelationship between dental fluorosis and enfiTriceuse: The aüthors iâêiiliIie õii1y tWlrfa-e ar , 00

brushing with fluoride containing dentifrice priorto 25 months of age and prolonged use of infantformula beyond 13 months of age, as beingsignificantly associated with dental fluorosis in afluoridated community.

More recent studies specifically addresseddentifrice use in more -detail, with most finding arelationship between early dentifrice use and dentalfluorosis21,62,66.80.Moreover, other studies have usedcase control methods to assess the relationshipbetween dental fluorosis and the early use of fluoridedentifrices. All these studies have demonstratedsi~ficant relationships between fluoride dentifriceuse àiíd dental fluorosis. A study of 157 patients~--- -aged 8~17-years attending a university pediatricdentistry clinic in Iowa City identified exposure tofluoride water and ~~oride dentifrice as risk factorsfor dental fluorosib A larger study of a similardesign was conducted in a pediatric dental practicein Asheville, North Carolina". This study found thatinitiating tooth brushing with fluoride dentifriceprior to age two was significantly associated withdental fluorosis. In addition, for those drinking non-fluoridated water, daily fluoride supplement use wasstrongly associated with dental fluorosis.

Of particular interest are a series o , -:- -designedcase control studies conducted by,Pendr)l and co-workers74.76.78 in both fluoridated-ând non-fluoridated areas in New England In these studies,parents completed detailed, self-administeredquestionnaires regarding infant feeding patterns,

..;

BUZAIAF, M. A. R.; CURY, J. A.; WHITFORD, G. M.FLUORIDEEXPOSUKESANDDENTALFLUOROSIS: A UTERATUREREVIEW

residence history, fluoride supplement use, brushing(with fluoride dentifrice) frequency, and amount ofdentifrice used per brushing up to eight years ofage. Among residents in fluoridated areas, mild-to-moderate dental fluorosis was associated with(inappropriate) supplement use, frequent brushingprior age of eight, and use of larger than pea-sizedamounts of dentifrice. The estimated percentage ofcases of dental fluorosis attributable to greaterdentifrice use was~l %7,77, (Pendrys et al. 1994,1995),

Among residents of non-fluoridated areas,Pendrys; Katz" found that mild-to-moderate dentalfluorosis was strongly associated with fluoridesupplement use and high household income, but theuse of infant formula and fluoride dentifrice werenot associated with increased risk for fluorosis.However, a later study " identified fluoridesupplement use and frequent, early toothbrushinghabits as significantly associated with mild-to-moderate fluorosis in both early and late enamelforming surfaces in the permanent teeth.

As a follow up to their trial of low fluoridedentifrice in children between the ages of three t0cltfive years in a fluoridated area!" Holt and co~workers40 compared the prevalence o dentalfluorosis amo'ilg high (1,055 ppm fluoride) andlow(550 ppmfluoriâe)IluorKIedentifrice grou s, w enchildren werê 9-10 years õf agti: 'Í'hi§~yJQ.l!!!.<!that use of fluoride supplements and use of standarddentifrice (1,055 ppm fluofiêie)"significantlyincreased the riskof deiiial Tluorosfâ'If t e-- -----permanent teeth.""'"tff1heir study of eight-year-old Norwegian

children whose water was not fluoridated, Wang andco-workers'P identified regular supplement use anduse of fluoride toothpaste prior to age 14 months asthe only significant risk factors for dental fluorosis.

Rock; Sabieha'" conducted a study of 325 8-9-year-old children living in optirnally-fluoridatedBirmingham, England and found a strongassociation between fluorosis in the maxillarycentral incisors and early dentifrice use and use ofdentifrice with a high (1,500 ppm ) fluorideconcentration. J1: was also observed that-a_higher~pro ortion of children without fluorosis had used a .~'---~'---~77~--~--77~~~~commercially available lQF:fulOride dentifnce. -" While case control methodologies, more âetalledsurvey instruments, and multivariate analysis usedin many of these recent studies lend more credenceto the conclusions than the earlier studies, ali of thesestudies have relied on retrospective assessment offluoride exposures, often eight to ten years after the

exposures had occurred. Thus, ali studies relatingdentifrice use to dental fluorosis are prone to recallbias. Nevertheless, there is now compelling evidence ~\/(that tlie early use of fluoride dentifrice is ª1! 1\inWOrtant risk factor for dental fluorosis, as youngêIíIl ren swa ow conSI era le amounts ofdentifrice. In fact, the amount of fluoride ingested!smversely related to the age of the child.

Dentifrices with a fluoride concentration of 1,000ppm contain 1.0 mg of fluoride per gram. In childrenyounger than 6 years of age, the mean quantity ofdentifrice per brushing episode is about 0.55 g86,corresponding to a fluoride exposure of about 0.55mg. An average of 48% of thi~Q.unt is ingestedby2-to 3-year olds, 42% by 4-year-olds and 34%by 5-year=0Ids5,20,38,86.Assuming mean bod weightsof 15, 18 -and~20kg;-respectively, fluoride intake

~ one rusmng per ay resITlls ün.'ngesttmrof-18, 13 and 9 mglkglday, respecti vely. So, it is evidentthat toothbrushing substantially Íncreases thefluorioeexposure, particularly for 2- to 3-year-o o......---- - --- -------children, and, of course, especially for children that6ríish more thãii-onCFâaily31:1riformation life thIsfor economically developing countries is rare".Studies conducted with 2-3-year-old Brazilianchildren, that lived in areas with fluoridated water,showed that they ingested 0.061 mg fluoride/kgbody weight per day (range 0.011-0.142) fromdentifrice" and that dentifrice contributed with 55%of the total amount of fluoride ingested daily". 1/(

Based on these findings, it is c1ear that measuresto reduce fluoride intake by children at risk o enfuor~~e n~essary. Two ~t~matives have beensuggestecCTnelrSt one would be to reduce theamount of dentifrice used. This is an importantmeasure, but we cannot forget that nowadays in mostfamilies both parents work and people who take careof the children not always follow parents'instructions. In addition, the fla vor of most childr.eJJdentifrices e~ages in estion. Because of this,It as een proposed that dentifrices with lowerfluoride concentrations should be developed andmarketed for use by young children, as has beendone in many countríesv" . The European Academy -;r:. X r'

of Paediatric Dentistry" advises the use of a very -~\) ..,small amount of low fluoride dentifrice from 6 ~~ li\]months to 2 years of age and the use of a pea-sized ( {j ,amount of 500 ppm fluoride twice daily from 2 to 6 Vyears. A higher fluoride concentration dentifrice(1,000-1,500 ppm) should be used as soon as thefirst permanent molars erupt. However, in somecountries (like Brasil and USA) the sale of lowfluoride dentifrices is not aliowed untillarge clínical

Rev.FOBV.9, n.112, p.I-IO,jan./jun. 2001

tn s have demonstrated safety and efficacy. It is-<-----~le that reducing the fluoride concentratio oLdenttfrices could reduce the anti-cari~ _ _ _--..:~-,-=-=-......;.:.::....co.-..;..-,=~.effectiveness. Therefore, the ideallower fluoride"'---I dentifrice should not only reduce fluoride ingestion,but also be equally effective in caries prevention ascurrently marketed formulations of 1,000-1,100ppm fluoride. Some researchers have developed lowfluoride formulations (550 ppm, NaF) that were aseffective as the "gold-standard" Crest (1,100 ppm)in terms of reducing enamel demineraliza~OI? and

jenhancing enamel remineralization in sit~ Thecariostatic effecti veness of this formulation,however, has not yet been tested in longitudinalclinical studies.

There have been many longitudinal clinical trialsofthe effectiveness of dentifrices with lowerfluorideconcentrations. Some of them found no significant

IJ differences between standard (1,000-1, 100ppm) and:4 low fluoride dentifrices (250-550 ppm~ fluoride )32,35,47. In contrast, Reed83, Mitropoulos and

,~ co-workers" and Koch and co-workers" found ther-. low-fluoride dentifrices to be somewhat less'- ~ effective than the 1,000 ppm dentifrices.

~t~ce, these studies might suggest thatlow-fluoridê dentifrices are less effective in termsof caries prevention than standard 1,000 ppmdentifrices. However, of these studies, only one"was conducted on the appropriate, preschool agegroup. This study did not find a statisticallysignificant difference between 250 ppm and 1,000ppm dentifrices. In view of the negative results ofthe studies cited above, however, it may be that afluoride concentration of 250 ppm is too much of adeparture from the standard 1,000 ppm dentifrice.A more practical formulation may have ~rideconcentrations in the range of 500-550 pp~

~

The only study of low-fluoride dentifrice that. used both a sample of young, preschool children

and a 500-550 ppm 1Ôtifrice was reported byWinter and co-workerU This three-year, doubleblind trial compared effectiveness of 550 and 1,055ppm fluoride dentifrices in children who were twoyears of age at baseline by measuring dmfincrements. The caries increment was slightly higher(I 0%) in the low-fluoride dentifrice group after threeyears, but the difference was not statisticallysignificant. The authors concluded that "the lowfluoride toothpaste possessed a similar anticariesactivity to the control paste and could therefore berecommended for use by young children." However,their conclusion was based on a single study andadditional trials of such dentifrices should be

conducted.Thus, even without corroborating studies, it

ap~a(the bestbâ1ãiiCeõetween prevention ofcaries and dental fluorosis favors reducedcC:Ucentrations of about 500-550 ppm fluoride QL.

~lefS:-However, those groups or individualsjudged to be at increased risk for dental caries mighthave a more favorable benefit/risk ratio with the useof standard 1,000-1,100 ppm fluoride dentifrices.While additional studies are needed for youngchildren that are not at high risk for caries but maybe at risk for dental fluorosis, it is appropriate toconsider recommendations that dentifricescontaining 500-550 ppm fluoride be marketed andendorsed for use by preschool children.

Any decision taken by official health organsshould take into account both anti-carieseffectiveness and risk for dental fluorosis. Inaddition, official health organs should reviewlabeling requirements for dentifrice to make thefluoride concentrations more apparent and shouldformulate guidelines for instructions regardingprudent use in young children. The SupportAgencies should finance additional well-controlledc' .cal trials oflow- fluoride dentifrices of sufficient'auration and follow-up to assess both dental caries'ãiiã fluorosis prevention. Such trials should bé"'éõnducted with populations of children in thetargeted preschool age group. Furthermore,manufacturers should be encouraged to aggressivelymarket dentifrice dispensers with small orifices orfixed amount "pumps" for use by young children.They should be encouraged or required also to warnparents concerning excessi ve use and ingestion ofdentifrices flavored for children. Dentists,physicians, and other professionals, as well asdentifrice manufacturers should continue torecommend the use of a small "pea-sized" amountof dentifrice (no more than 0.25 g) for youngchildren. In addition, preschool children should bewell-supervised in their use of fluoride dentifrice,and the dentifrice should be placed on a child-sizetoothbrush by a parent or other adult'?'.

Infant foods and drinks

During infancy the main sources of fluoride areconsidered to be commercially available foods andbeverages. Many studies have shown that thefluoride concentrations of infant foods andbeverages span a wide range and depends mainlyon the fluoride concentration in the water used tomanufacture them29,30, 106.

BUZALAF, M. A. R.; CURY, J. A.; WHITFORD, G. M.FLUORIDEEXPOSURESANDDENTALFLUOROSIS:ALlTERATUREREVIEW

Beikost is a collecti ve term for foods other thanmilk or formula fed to infants. The fluorideconcentration of most beikost is quite modest".However, some cereals in Brazil have been shownto have higher fluoride concentrations than wouldbe expected. This was lhe case for Mucilon andNeston, both manufactured by Nestlé, which hadfluoride concentrations of 2.44 and 6.2 ppm,respecti vely. A relati vely high fluoride concentrationwas also found in a ready-to-drink chocolate milk(1.2 ppm, Toddynho, Quaker). When one of theseproducts is consumed just once a day it can provideas much as 25% of lhe fluoride intake believed tobe associated with increased risk for dental fluorosisof esthetic concern (0.1 mg F/kg body weightlday)for a 2-year-old child". Of especial concem are alsosome teas, especially the black tea (Camelliiasinensis), which has high fluoride concentrations".Thus, these products may be important contributorsto total daily fluoride intake and their consumptionby children at lhe age of risk for dental fluorosismust be controlled". In addition, the manufacturersshould inform the fluoride content on the label.

RESUMOa declínio na prevalência e incidência de cárie

dentária nas duas últimas décadas é considerado serdevido, em grande parte, ao amplo uso do flúor.Entretanto, a prevalência de fluorose dentáriaaumentou simultaneamente. a aumento foi nasformas de fluorose suave e muito suave, tanto emáreas fluoretadas como não fluoretadas. Uma grandequantidade de dados epidemiológicos mostra que aocorrência de lesões fluoróticas está associada àingestão excessiva de flúor durante o período dedesenvol vimento dental. Muitas fontes de flúor têmsido identificadas. Esta revisão descreve a condiçãoe sumariza a literatura recente acerca dos fatores derisco para fluorose dentária. Quatro fatores de riscomaiores foram consistentemente identificados: usode água fluoretada, suplementos de flúor,dentifrícios fluoretados ou fórmulas infantis. Emadição alguns alimentos e bebidas manufaturadospodem ser importantes contribuintes para a ingestãodiária total de flúor.

lJNITERMOS: Flúor; Fluorose dentária, risco.

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IV;mn~:::K=LD::~::~~=:'llmlm:1J:::::.,::~;::::::~=)JIand dental caries V. Additional studies of the relation Fluoride concentration in infant foods and risk of dentalof fluoride domestic waters to dental caries experience fluorosis. J. dent. Res., v. 80, p. 224, 2001. Specialin 4,425 white children aged 12-14 years in 13 cities in Issue. Abst 1505.4 states. Pubüc HeaIth Rep., v. 57, p. 1155-79, 1942.

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Corresponding author:

MARÍLIA AFONSO RABELO BUZALAFAI. Octávio Pinheiro Brisolla, 9-75Departamento de Ciências BiológicaslBioquímicaBauru-SP Brazil17012-901e-mail: mbuzalaf@fob.usp.br