1. T he 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 fluorosis
is associated with exeessive fluoride intake throughout the period oftooth development. Multiple sources of
fluoride intake have been identified. This review deseribes the condition and summarizes the recent literature
on the risk faetors for dental fluorosis. Four major risk faetors have been eonsistently identified: use of
fluoridated drinking water, fluoride supplements, fluoride dentifrice and infant formulas. In addition, some
manufaetured ehildren foods and drinks may also be important contributors to total daily fluoride intake.
UNITERMS: Fluoride; Dental fluorosis, risk.
p <"4~f~ f LJ-DPJ:6u
INTRODUCTION the recent literature on risk factors for dental
fluorosis.
J:here has been a decline in dental caries r Dental fluorosis is a fluoride- induced disturbance
prevalence and incidence durin the last two in tooth formation, which results in hypomineralized
decades both in economicali develo d36,60,61,69 and , enamel with increased porosity". It is caused by
in economicaliy developing countries37,67, This107. I excessive fluoride intake but only during the period
I
Jige~se is considered to be largely due tolhe of tooth development'v'v'<". The most important
~.§pr:ead use of fluoride. Concurrent with the risk factor for fluorosis is the total amount of fluoride
~ decline in caries, an increase in the revalence of consumed from ali sources during the critical period
dental fluorosis has been documented, in of tooth development' 5.17,3 . 1.63
êommunities with43,55,101,103 without fluoridated
and The clinical appearance of mild dental fluorosis
arrnking water43,55.80.101.
Concem with the increase is characterized by bilateral, diffuse (not sharply
in the prevalence of fluorosis has led to many studies demarcated) opaque, white striations that run
on the reasons for the increase, and in identifying horizontally across the enamel. These may be
the important risk factors. These studies have had invisible to the individual and the clinician but often
different designs and employed different can be seen after the enamel has been dried. The
populations, many with multiple sources offluoride opacities may coalesce to form white patches. In
exposure. Further, they have used different indices the more severe forms the enamel may become
to diagnose and score dental fluorosis. This has discolored andlor pitted24,26,97,98. eruption into
Upon
made it difficult to compare the results of these the mouth, fluorosed enamel is not discolored - the
studies. The purpose of this review is to summarize stains develop over time due to the diffusion of

2. ___ o
BUZALAF, M. A. R.; CURY, J. A.; WHITFORD, G.M.
FLUORIDEEXPOSURESANDDENTALFLUOROSIS:AUTERATUREREVIEW
exogenous ions (eg, iron and copper) into the per day as the exposure level above which dental
abnormally porous enameL fluorosis occurs", although studies in Kenya have
~e~ underlyin the de elQ me..!!!.Q[ found fluorosis with a daily fluoride intake of less
dental fluorosis lias not been conc1u~ely than 0.03 mg Flkg body weight per day from
~as believed previously that water-". In these latter studies, however, the teeth
éxCesslve fliíoride intake interfered with the function were dried in order to detect the mildest forms of
of ameloblasts, perhaps inhibiting the secretion of, fluorosis. A daily fluoride intake between 0.05 and
or altering the composition of enamel matrix 0.07 mg/kg "ooây-weiglit -peidãy is generall y
proteins. lt now appears that this is unlikely for regarded as optimum for prevention of dental
several reasons inc1uding the fact that the risk of caries?". Other factors that may increase the
dental fluorosis is lowest during the secretory stage Susceptibility of indi viduals to dental fluorosis are
of enamel development 16,17,27,28. altitudel.42,57.59.93,1I0,111,114, SeM
renal insufficiency45,46,82,104, d '.!~I
,..
Microscopically, the structural arrangement of and malnutrition?':'!". Some of these~, .-
the crystals appears normal, but the width of the however, can produce enamel changes tha~~~ble
intercrystalline spaces is increásed,@!ng po~ dental fluorosis in the absence of signíficant
The degree and extent of porosity depends on the exposure to fluoride. ~
concentration of fluoride in the tissue fluids during Studies of dental fluorosis, done in areas Wi~
tooth development25.I02 ln fac, e risk of dental and without fluoridated drinking water, have
fluorosis base on animal shidies, is directl~ identified four major risk factors: use of fluoridated
'-<o the interaction o clrculatlllg fIuoru e drinking water, fluoride supplements, fluoride
coíiêêiitrations and time, fe:'- the area under the time- dentifrice, and infant formulas before the age of
concentration curve Thus it appeãrs that dental seven years. Some manufactured children foods and
~
fluorosis can result from a range of plasma fluoride drinks may also be important contributors to total
concentrations provided that they are maintained for daily fluoride intake.
sufficientl y long periods 111With increasing severity
.
of fluorosis, the fluoride concentration throughout Fluoridated drinking water
the enamel, the depth of enamel involvement, and
the degree of porosity also íncreases"-". Clinical Dean 14, n 1942, stated that some 10% of children
i
studies of dental fluorosis have demonstrated that in optimally fluoridated (1.0 ppm) areas were
/"...---- - -- - -.---
the most critical period for efevelopment of fluomsís
- affected by mild or very mild fluorosis in the
ís during thê õSf-secr:eto"ry or early maturati2!!- permanent teeth and that less than 1% were so
phase of tooth development 2;26-;52;7~:S4,J(J~ affected in low-fluoride areas. These degrees of ri A~n S
; Fluorosis islesãprêvalent and le;-apparent in prevalence were recorded p@~ the availability
prirnary teeth than in permanent teeth, and, in any of fluoridated dental products when fluoridated
case, fluorosis of the prirnary teeth has only short- drinking water was the only significant source of
term rather than long-term consequences. Therefore, fluoride intake-". In North America, the prevalence
the major concern about fluorosis is with the of dental fluorosis now ranges between 7.7% to 69%
permanent teeth. Since the different permanent teeth in fluoridated communities, and from 2.9% to 42%
~ atmfferent~~'period in non-fluoridated communities. The studies done
~.e den@~ ex.!.~nds frol!1eleven mc:nths after the 1980s have shown the highest prevalences'".
The studies by Spuznar; Burt'? and Riordan" are in
---- -----
to seven years of ag~ The permanent maxillary
--- _-
..- ..
central incisors are of greatest cosmetic importance agreement that the risk of fluorosis in areas where
ánd they appear most at risk of fluorosis between the water fluoride concentration is 0.8 ppm is four
ages of fifteen and twenty-four months for males" times higher than in non-fluoridated
ãiíQ-oetween fwenty-oiiê"ãiid thiity moº~s fm- communities'T'=". However, water fluoride
,females23. Howéver:ãmeta-analysis of the risk probably has its greatest impact on fluorosis
periods ássociated with the development of dental prevalence indirectly, through being used in the
fluorosis in maxillary permanent central incisors processing of infant formulas, other children' s foods
showed that the duration of excessi ve fluoride and soft drinks". ln a systematic review of 214
exposure throughout amelogenesis, rather than studies on water fluoridation, McDonagh et al.?'
specific risk periods, would seem to explain the observed an increase in the proportion of caries-
development of dental fluorosis". free children and a reduction in the number of teeth
Some authors regard to 0.1 mg Flkg body weight affected by caries. They also noted a dose-dependent

3. Rev.FOB
V.9, n.1/2, p.1-10,jan./jun. 2001
increase in dental fluorosis. At a fluoride level of 1 fluoridated water, they provide a daily fluoride
ppmin the drinking water, they estimated that 12.5% intake above that likely to cause some degree of
of exposed people would have fluorosis that they dental fluorosis'<". Therefore, to reduce the risk of
would find of esthetic concem, a prevalence much fluorosis the recommendation is to use ready-to-
higher than that reported by Dean 14in 1942 who feed formulas whose fluoride concentrations are
~--
found virtually no cases of moderate or severe known to be low, or low-fluoride bottled water to
/>«: _
fluorosis. The present-day prevalence of fluorosis dilute the formula concentrate.-- ~
indicates ~~g c~~tíng
.;-----
waer.
- ----------
:f:1ÍÍÔfidefromsources in aaartíOi1to tha~Lllg Fluoride dentifrice
Ripa" reviewed studies that investigated the
" . Dietary fluoride supplements possible association between the use of fluoride
dentifrice and prevalence of dental fluorosis. He
Fluoride supplements are recommended for concluded that of the ten studies reviewed,
children living in fluoride deficient areas. The nine7.9.18.39,49.74,96.99,113 find an association.
failed to
recommended dai1y dose is based on the age of the These studies, however, were not designed with
child and on the fluoride concentration in the fluoride dentifrice effects as the major focus 01' used
drinking water. However, there are many reports surrogate measures to evaluate fluoride dentifri[;~
showing that supplements are prescribed exposure.From this group of studies, the only oniV
inappropriately to children in fluoridated used case control methodologles to assess t e
areasS1,7S,100.
Many studies have identified fluoride relationship between dental fluorosis and enfiTrice
supplements as risk factors for dental fluorosis, both use: The aüthors iâêiiliIie õii1y tWlrfa-e ar , 00
in fluoridated+":" and non-fluoridated areas40,43,49. brushing with fluoride containing dentifrice prior
"'< Sl,74,7S.IOS.fluoridated areas the risk of dental
In to 25 months of age and prolonged use of infant
~ fluorosis from use of fluoride supplements is almost formula beyond 13 months of age, as being
~ 4 times higher than in non- flu2.ti.da~ed af_t:.as63,S7. significantly associated with dental fluorosis in a
~ ~e, the risk of dental fluorosis from the use of fluoridated community.
fluoride supplements is well established. Clinicians More recent studies specifically addressed
must be sure of the water fluoride concentrations, dentifrice use in more -detail, with most finding a
âSWell as of the caries risk of the child, before relationship between early dentifrice use and dental
preSciibing fluori e supplements. The U.S. Centers fluorosis21,62,66.80.
Moreover, other studies have used
1OfOlsease . onlíOl an revention has recently case control methods to assess the relationship
Qublished uidelines for the judicious rescription between dental fluorosis and the early use of fluoride
?f dietary fluoride su lements 11. dentifrices. All these studies have demonstrated
si~ficant relationships between fluoride dentifrice
Infant Formulas use àiíd dental fluorosis. A study of 157 patients
~--- -
aged 8~17-years attending a university pediatric
Because of its very low fluoride contcentration, dentistry clinic in Iowa City identified exposure to
human breast milk is a poor source of fluoride. In fluoride water and ~~oride dentifrice as risk factors
infancy the major source of fluoride is considered for dental fluorosib A larger study of a similar
to be infant formulas. A number of studies have design was conducted in a pediatric dental practice
implicated the consumption of infant formulas as a in Asheville, North Carolina". This study found that
risk factor for dental fluorosis, particularly in initiating tooth brushing with fluoride dentifrice
fluoridated areaslO.44·S3.71,SS,94,10S, in non-
but not prior to age two was significantly associated with
fluoridated áreas". Soy-based formulas have been dental fluorosis. In addition, for those drinking non-
reported to have-sDmewhat high~:t:l.!liiíide_ fluoridated water, daily fluoride supplement use was
êóncenfrations than milk-based formulas 1 OS 0,94.1and strongly associated with dental fluorosis.
'this has been attribí.ife~~er end~~~ls Of particular interest are a series o , -:- -designed
Õf1-1iíõfidem the soy extract44·54.65. However, the case control studies conducted by,Pendr)l and co-
most important factor when considering infant workers74.76.78 in both fluoridated-ând non-
'formUlãS-as risk'factors for dental fluorosis isthe fluoridated areas in New England In these studies,
water used to reconstitute them. When infant parents completed detailed, self-administered
formulas are recorisfitutedwith optimally questionnaires regarding infant feeding patterns,
..;

4. BUZAIAF, M. A. R.; CURY, J. A.; WHITFORD, G. M.
FLUORIDEEXPOSUKESANDDENTALFLUOROSIS: A UTERATUREREVIEW
residence history, fluoride supplement use, brushing exposures had occurred. Thus, ali studies relating
(with fluoride dentifrice) frequency, and amount of dentifrice use to dental fluorosis are prone to recall
dentifrice used per brushing up to eight years of bias. Nevertheless, there is now compelling evidence ~/(
age. Among residents in fluoridated areas, mild-to- that tlie early use of fluoride dentifrice is ª1! 1
moderate dental fluorosis was associated with inWOrtant risk factor for dental fluorosis, as young
(inappropriate) supplement use, frequent brushing êIíIl ren swa ow conSI era le amounts of
prior age of eight, and use of larger than pea-sized dentifrice. In fact, the amount of fluoride ingested
amounts of dentifrice. The estimated percentage of !smversely related to the age of the child.
cases of dental fluorosis attributable to greater Dentifrices with a fluoride concentration of 1,000
dentifrice use was~l %7,77, (Pendrys et al. 1994, ppm contain 1.0 mg of fluoride per gram. In children
1995), younger than 6 years of age, the mean quantity of
Among residents of non-fluoridated areas, dentifrice per brushing episode is about 0.55 g86,
Pendrys; Katz" found that mild-to-moderate dental corresponding to a fluoride exposure of about 0.55
fluorosis was strongly associated with fluoride mg. An average of 48% of thi~Q.unt is ingested
supplement use and high household income, but the by2-to 3-year olds, 42% by 4-year-olds and 34%
use of infant formula and fluoride dentifrice were by 5-year=0Ids5,20,38,86. Assuming mean bod weights
not associated with increased risk for fluorosis. of 15, 18 -and~20 kg;-respectively, fluoride intake
However, a later study " identified fluoride ~ one rusmng per ay resITlls ün.'ngesttmrof-
supplement use and frequent, early toothbrushing 18, 13 and 9 mglkglday, respecti vely. So, it is evident
habits as significantly associated with mild-to- that toothbrushing substantially Íncreases the
moderate fluorosis in both early and late enamel
forming surfaces in the permanent teeth.
-
fluorioeexposure, particularly for 2- to 3-year-o
......---- --- -------
children, and, of course, especially for children that
o
As a follow up to their trial of low fluoride 6ríish more thãii-onCFâaily31:1riformation life thIs
dentifrice in children between the ages of three t0 for economically developing countries is rare".
five years in a fluoridated area!" Holt and co~
clt Studies conducted with 2-3-year-old Brazilian
workers40 compared the prevalence o dental children, that lived in areas with fluoridated water,
fluorosis amo'ilg high (1,055 ppm fluoride) andlow showed that they ingested 0.061 mg fluoride/kg
(550 ppmfluoriâe)IluorKIedentifrice grou s, w en body weight per day (range 0.011-0.142) from
children werê 9-10 years õf agti: 'Í'hi§~yJQ.l!!!.<! dentifrice" and that dentifrice contributed with 55%
that use of fluoride supplements and use of standard of the total amount of fluoride ingested daily". 1/(
dentifrice (1,055 ppm fluofiêie)"significantly Based on these findings, it is c1ear that measures
permanent teeth. -- -----
increased the riskof deiiial Tluorosfâ'If t e to reduce fluoride intake by children at risk o en
fuor~~e n~essary. Two ~t~matives have been
""'"tff1heir study of eight-year-old Norwegian suggestecCTnelrSt one would be to reduce the
children whose water was not fluoridated, Wang and amount of dentifrice used. This is an important
co-workers'P identified regular supplement use and measure, but we cannot forget that nowadays in most
use of fluoride toothpaste prior to age 14 months as families both parents work and people who take care
the only significant risk factors for dental fluorosis. of the children not always follow parents'
Rock; Sabieha'" conducted a study of 325 8-9- instructions. In addition, the fla vor of most childr.eJJ
year-old children living in optirnally-fluoridated dentifrices e~ages in estion. Because of this,
Birmingham, England and found a strong It as een proposed that dentifrices with lower
association between fluorosis in the maxillary fluoride concentrations should be developed and
central incisors and early dentifrice use and use of marketed for use by young children, as has been
dentifrice with a high (1,500 ppm ) fluoride done in many countríesv" . The European Academy -;r:. X r'
concentration. J1: was also observed that-a_higher~ of Paediatric Dentistry" advises the use of a very -~) ..,
pro ortion of children without fluorosis had used a . small amount of low fluoride dentifrice from 6 ~~ li]
~'---~'---~77~--~--77~~~~
commercially available lQF:fulOride dentifnce. - months to 2 years of age and the use of a pea-sized ( {j ,
" While case control methodologies, more âetalled amount of 500 ppm fluoride twice daily from 2 to 6 V
survey instruments, and multivariate analysis used years. A higher fluoride concentration dentifrice
in many of these recent studies lend more credence (1,000-1,500 ppm) should be used as soon as the
to the conclusions than the earlier studies, ali of these first permanent molars erupt. However, in some
studies have relied on retrospective assessment of countries (like Brasil and USA) the sale of low
fluoride exposures, often eight to ten years after the fluoride dentifrices is not aliowed untillarge clínical

5. Rev.FOB
V.9, n.112, p.I-IO,jan./jun. 2001
tn s have demonstrated safety and efficacy. -<----- It is conducted.
~le that reducing the fluoride concentratio oL Thus, even without corroborating studies, it
~denttfrices could reduce
_ _ the anti-cari
_--..:~-,-=-=-......;.:.::....co.-..;..-,=~. ap~a(the bestbâ1ãiiCeõetween prevention of
effectiveness. Therefore, the ideallower fluoride caries and dental fluorosis favors reduced
"'---
I dentifrice should not only reduce fluoride ingestion, cC:Ucentrations of about 500-550 ppm fluoride QL.
but also be equally effective in caries prevention as ~lefS:-However, those groups or individuals
currently marketed formulations of 1,000-1,100 judged to be at increased risk for dental caries might
ppm fluoride. Some researchers have developed low have a more favorable benefit/risk ratio with the use
fluoride formulations (550 ppm, NaF) that were as of standard 1,000-1,100 ppm fluoride dentifrices.
effective as the "gold-standard" Crest (1,100 ppm) While additional studies are needed for young
in terms of reducing enamel demineraliza~OI? and children that are not at high risk for caries but may
enhancing enamel remineralization in sit~ The be at risk for dental fluorosis, it is appropriate to
cariostatic effecti veness of this formulation, consider recommendations that dentifrices
j however, has not yet been tested in longitudinal containing 500-550 ppm fluoride be marketed and
clinical studies. endorsed for use by preschool children.
There have been many longitudinal clinical trials Any decision taken by official health organs
ofthe effectiveness of dentifrices with lowerfluoride should take into account both anti-caries
concentrations. Some of them found no significant effectiveness and risk for dental fluorosis. In
IJ differences between standard (1,000-1, 100 ppm) and addition, official health organs should review
:4 low fluoride dentifrices (250-550 ppm labeling requirements for dentifrice to make the
~ fluoride )32,35,47. In contrast, Reed 83, Mitropoulos and fluoride concentrations more apparent and should
,~ co-workers" and Koch and co-workers" found the formulate guidelines for instructions regarding
r-. low-fluoride dentifrices to be somewhat less prudent use in young children. The Support
'- ~ effective than the 1,000 ppm dentifrices. Agencies should finance additional well-controlled
~t~ce, these studies might suggest that c' .cal trials oflow- fluoride dentifrices of sufficient
low-fluoridê dentifrices are less effective in terms 'auration and follow-up to assess both dental caries
of caries prevention than standard 1,000 ppm 'ãiiã fluorosis prevention. Such trials should bé"
dentifrices. However, of these studies, only one" 'éõnducted with populations of children in the
was conducted on the appropriate, preschool age targeted preschool age group. Furthermore,
group. This study did not find a statistically manufacturers should be encouraged to aggressively
significant difference between 250 ppm and 1,000 market dentifrice dispensers with small orifices or
ppm dentifrices. In view of the negative results of fixed amount "pumps" for use by young children.
the studies cited above, however, it may be that a They should be encouraged or required also to warn
fluoride concentration of 250 ppm is too much of a parents concerning excessi ve use and ingestion of
departure from the standard 1,000 ppm dentifrice. dentifrices flavored for children. Dentists,
A more practical formulation may have ~ride physicians, and other professionals, as well as
concentrations in the range of 500-550 pp~ dentifrice manufacturers should continue to
The only study of low-fluoride dentifrice that recommend the use of a small "pea-sized" amount
. used both a sample of young, preschool children of dentifrice (no more than 0.25 g) for young
and a 500-550 ppm 1Ôtifrice was reported by children. In addition, preschool children should be
~ Winter and co-workerU This three-year, double well-supervised in their use of fluoride dentifrice,
blind trial compared effectiveness of 550 and 1,055 and the dentifrice should be placed on a child-size
ppm fluoride dentifrices in children who were two toothbrush by a parent or other adult'?'.
years of age at baseline by measuring dmf
increments. The caries increment was slightly higher Infant foods and drinks
(I 0%) in the low-fluoride dentifrice group after three
years, but the difference was not statistically During infancy the main sources of fluoride are
significant. The authors concluded that "the low considered to be commercially available foods and
fluoride toothpaste possessed a similar anticaries beverages. Many studies have shown that the
activity to the control paste and could therefore be fluoride concentrations of infant foods and
recommended for use by young children." However, beverages span a wide range and depends mainly
their conclusion was based on a single study and on the fluoride concentration in the water used to
additional trials of such dentifrices should be manufacture them29,30, 106.

6. BUZALAF, M. A. R.; CURY, J. A.; WHITFORD, G. M.
FLUORIDEEXPOSURESANDDENTALFLUOROSIS:ALlTERATUREREVIEW
Beikost is a collecti ve term for foods other than REFERENCES
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~:::K=LD::~::~~=:'llmlm:1J:::::.,::~;::::::~
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