Oral fluoride retention after uso of fluoride dentifrices


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Oral fluoride retention after uso of fluoride dentifrices

  1. 1. © 1991 S. Karger AO, Basel 0008-6568/9110252-0123 s 2.75/0 Cafies Res 1991 ;25: 123-129 R.M. Duckworth, S.N. Morgan Unilever Dental Research, Unilever Research Port Sunlight Laboratory, Bebington, UK Key Words. Dentifrice Fluoride· Kinetics· Monofluorophosphate, Oral f1uoride retention· Reservoir· S,divary clcara ncc Abstract. Fluoride is the only extensively clinically proven means of reducing dental cáries. Despire a !arge bodyof epidemiological data on the effectiveness of t1uoride, delivered in the form of dentifrices, mouthrinses, drinking water, etc., the precise mode of action of fluoride is not completeIy understood. The purpose of this p.lperis to report an investigation ofthe link between oral f1uoride levels and applied f1uoride dose from denti- rriCt:~, Hum an sulivary fluoride clearance studies and equilibrium baseline studies 01 fluoride in saliva and plaquc have been carried out with denti~rices whicl: con~ained 1,0?O, I ,50? ~nd 2,5?0 ug fluo~ide per gram as, sodium monofluorophosphate, After a single brushing with a fluonde dentifrice, salivary fluonde decreased 111 1110 distinct phases: an initial rapid phase which lasted for 40-80 min, depending on the individual, and a sec- ond slaw phase !asting for severa! hours. The Jatter phase is be!ieved to be due to fluoride released from an ora! Ouoride reservo ir. During regular repeated use ofthe test dentifrices, the equilibrium baseline f1uoride concen- ralion, attained in both saliva and plaque between one application and the next,increased significant!y com- pared with placebo values. Such e!evated baseline fluoride concentrations also increased with increasing Na:FP03 content 01 the dentifrices. The presentwork supports the concept that labile f1uoride, stored in an oral [luoride reservoir at the time oftreatment application, may maintain a prolonged protective effect against dental caries. Many countries have experienced dramatic reduc- et aI., 1986; Goorhuis and Purdell-Lewis, 1986; / . , lions in caries prcvalence ave r the past 15 years or so. Schâfer, 1989]. Saliva is supersaturated with respect to "fhese reductions have often been related to lhe regu- the hydroxyapaÚte of tooth ename! and is a source of lar use ar flu(jii~·e (entífIices [Murra} and Rugg- c~lciu;n-and phClSpnat ·OU~ (o tbe_re ir õ(ear.ly Gunn, 1982~ Matthtilet;· enson er ai., 985; enarnel lesions. Rolla and @gaatd,. i987}, the niajolity af which con- Certain authors have suggested that fluoride, even !aio sodium tiidtiôfluotophos hate and/or .!odium at low concentrations, Ís necessary in the oral fluids to nuori as the s0utces of uQÜde. õbtain rnaximum caries inhibition and have con- Despite the large arnount of epidemiological data e udedth<rt continuous or frequent elevation of the on the anticaries effectiveness of fluoride, the precise mode of action of fluoride is not completely under- --- flu;ride concentratiõOin ~ the orãIfluid; - -- y"antageous [Fejerskov et al., 1981; Ekstrand wouTclbeãd: -- ---; et aI., stood. There is 3ubstantial evidcnce that the presence 1986; Featherstone et al., 1986}. The retention offluo-I of fluorÍde ili the í1louth encourages the remíneraliza- ride in the mouth after application of dentalprodUctsI t~ar1 I lesiens [Gelharc.! and Arends, 1984; Mell- sucl;aSdentífr~ and ~OUthwashes may be asso- berg et al., 198$, 19S6; COrprOJ1 et al., 1986: de Kloet çjl!kd wíth an oral fluoride reservoir. Such a reservo ir ma serve as a store for fluoride which reIeases its J We thank DI. P.T. Whittall for assistance with cornputer pro- co teIl!..s into saliva gradually and thereby potentially gramming. ,---. rnaintains a degres of protection against caries for a - :.~ ,.. .. . , . .i ;
  2. 2. ·- 124 DuckworthiMorg~ I ~ .~I -------- --,~! ~ 60 l buffer using 1987J. Saliva samples previously described collected procedures [Duckworth witl in 3 h after dentifrice et apPhc". " ~I~ al ~ Uo tion v:ere either treated with perchloric ~cid 01 incubated at 37 C ~l.·,. 50 overnight morder to ensure that any FPOi ions were hydrolyzed Ia ffii o:> li> • F- before fluoride analysis, A feasibility study confírmed thlj I" 4-0 known arnounts of Na1FP03 added to whole saliva were COl1venld . p completely to r by lhe latter procedure (fig. I). " ~ 30 Oral Clearance Studies 11 7-10 adult subjects used a non-fluoride dentifrice at home fOral least 10 days prior to, and during, lhe experimental period For each test, lhe subjects brushed with 1,5 g test dcntifrice for I mio o spat out lhe dentifrice/saliva slurry, and then rinsed their mOUt~ E for 5 s with 10 ml distilled water twice. Mixed saliva samplc" . =:: li. 10 (> 0.8 ml) were collected both bcfore dcntifricc application and a; t regular intervals Cor several hours afterwards, At least 2 day! ~ " Q, ti:: O +--------.--------.-------r-----r-----, elapsed between applications er each test ?entifrice. Subjecis welt ~l O 5 10 15 20 25 asked not to drink tCJ 01 cal during iest pcriods, ~ Time, h "1 , R Equilibrium Study Fig. 1. Break down of FPO~ to F" in hurnan whole saliva incu- The protocol was similar to that of a previous study involving bated at 37°e. Nominal initial FPO~- concentration 52.6 umol/I mouthwashes [Duckworth et al., 1987J. Briefly, 7 adults used a nOno (I pprn F). Symbols refer to different experiments. fluoride dentifrice for at least 2 weeks prior to the use of the teM dentifrices. The subjects then brushed with each test dentifrice daily for about 4 weeks. Samples of saliva and plaque were collected once per week, at least 18 h after the last brushing. The subjccls prolonged period. Fluoride which is present in the were not exposed to any other high-fluoride dose during the study, íiiOiith in a labile form during a cariogenic challenge Curve Fiuing is JikeJy to be the most bcneficial. Both individual and mean oral fluoride clearance curves wcrc The work reported here seeks to determine whether fitted by computer (SAS PROC NLlN) using a non-lincar regres. the amount of l1uoride retained in the mouth is suffi- sion procedure [Marquardt, 1963] to the biexponential function cient to maintain a significantly elevated level of fluo- F, = A exp (-at) + B exp (-~t) ride between 01 e application of a dentifrice and the next. Oral fluoride studies have most often involved where F, is the salivary fluoride concentration at time t, and A, e, measurements ofthe fluoride content ofwhole-mouth B, and ~ are model parameters. In approximation A and B are lhe zero time intercepts, and a and ~ the slopes, of lhe first and second (rnixed) saliva and of plaque. In this work two types clearance phases of clearance curves respectively. Equation I is lhe of measurements have been rnade to investigate the solution for lhe so-called two-compartment open pharmacokinclic concentration of fluoride itUilli..Y.:J bét;ecn b[1lshing~ model originally applíed to lhe analysis of drug clcurance Crorn ~ - - ~it l-dentifoF-. Oral clearance studies have moni- tored the decrssse in fluoride concentration with time blood [Wagner, 1975J, Arcas under each clearance ues) were calculated using the equation curve (AUC vaI. after a single dentifrice application, whilst equilib- rium studies have monitored changes in the baseline AUC = S F, dt = A/a + B/~ (2) o fluoride concentration during regular, repeated use of dentifrices. The dentifrices used in the studies re- The half-lives of each clearance phase were calculated using the ported here contained sodium monofluorophosphate respective expressions tl/2 (I) = 0.693/a, and tl/2 (2) = 0.693/p. ! ~ . as the fluoride some. Results Materials arid Mefhods Salivary Fluoride Clearance The test dentifrices contained 1,000, 1,500, and 2,500 Ilg fluo- The shape of salivary fluoride clearance curves was ride per gram as Na)"POj in an alumina base and were identical to formulations tesred iü a 3-yeàl caries clinical trial [Stephen et al., similar after a single brushing with any of the denti. 1988], Fluoride conteuts of saliva and plaque were rneasured by frices tested. Typical mean data for 10 subjects who means 01 a fluoride lon: speciíic electrode in the presence ofTISAB had used a dentifrice containing 1,500 ug fluoride per
  3. 3. ... livaFluoride from Dentifrices 125 :;..-- .., r:lm as Na2FPO, are shown in figure 2. Total ionic 200 J _"-----,r , ~uoride co~centration .(F- +, FPO~- íons) is plot~ed on .dogarithmlc scale against time and decreased m two 100 ~o dlstinct phases. During the first phase, which !asted for 40-80 min depending on the individual, the mean i,;livary fluoride concentration decreased rapidly 1 A ~r(11!1a. 200 to ca. 4 umol/L During the second phase, c lhe salivary fluoride concentration decreased rela- I Iiely slowly and reached 0.95 umol/I after 3 h. As ,:1 part of the dose-response study mentioned below, 7 I 5ubjects used the same dentifrice and the average I, Ouoride concentration during the second c1earance p ase decreased to 0.58 umol/I after 6 h. 1.0 ! The comparison in figure 2 between the mean 0,5 --fl----~ ----,---------;,,-----~ ! e~perimental data points and the curve derived using o 50 100 150 200 ; quation 1 indicates that the chosen pharmacokinetic Time, min i modelis appropriate. The quality of fit was excellent Fig. 2. Mean salivary fluoride clearance curve after use of 1,500 (r" 0.999) and values of r2> 0.99 were consistently flg F/g NazFPOJ dentifrice (n = 10). O = Experimental data (bars observed for the individual c1earance data. = SD); - = computer-fitted model curve. Results for à dose-response study in which 7 sub- jects used each dentifrice are summarized in table I in Table 1. Dependence of clearance curve parameters on the ~ermsofthe model pararneters AUC and B. These pa- Na2FP03 content of dentifrices (mean ± SD; n = 7) meters are measures of the overall amount of fluo- ride in the mouth and the amount of fluoride asso- Na2FPO, ParameterB AUC t,12(1) t,nC2) ~iated with the second c1earance phase respectively. (F, ug /g) (F, umcl/I)" (mmol F/I- min)" rnin min Linear regression analysis showed the increase in 1,000 1.48 (+ 0.73) ]1.9J (+ 0.36) 9.1 ±2.2 244.9± 84.3 both parameters with increasing Na2FP03 content of (- 0.47) (- 0.30) dentifrices to be highly significant on an individual 1.88 (+ 0.85) 2.22 (+ 0,42) 9.0±2,4 1,500 197.2±50,0 basis (p<O.OOOi) The rnean AUC and B values for (- 0.57) (_. 0.35) lhe dentifrice with a fluoride content of 2,500 ~tg/g 2,500 3.03 (+ 1,43) 3.87 (+ 0.73) 6.5 ± 2-8 141.9 ± 34.8 IVere significantly difTerent from corresponding val- (- 0.98) (- 0.61) ues for the 1,000- and 1,500-flg F/g dentifrices a Values are antilogs of logarithmic mean values ofthc individual (P<0.02; analysis of variance). Furthermore, the ma- data. The 2,500-).1g/g values are significantly different from lhe ;ority of individual AUC (6/7) and B (517) values values connected by lhe bar (p < 0.02; analysis ofvariance). ~verehígher after use of the 1,500 ug FI g dentifrice -------------- than after use of the dentifrice with a fluoride content ,111,000 !lg/g. efespife the rrtean difference being not statistically significànt. AO mean B values were signif- oride derttifrices relative to a non-F control dentifrice. icantly above the mean baseline fluoride concentra- Figure 3 shows that the rnean salivary fluoride con- [iOIlof 0.46 !J.l1101/1 rneasured in saliva sarnples taken centration increased steadily to a plateau after about 2 before dentifrice application. The mean half-lives of weeks of daily brushing with the dentífrice containing each cleurance phase are also listed in table l. The 1,000 ug fluoride per gramo This pattern was repeated value of t 1/2 (2) for the 2,500-flg fluoride group was sig- with each dentifrice tested. When brushing with a flu- nificantly less than the corresponding value for lhe oride dentifrice stopped, the baseline salivary f1uoride grOUPusing a dentifrice with a Iluoride content 01 concentration returned to its original value which had !,OOO!J.g/g (p < 0.05). been attained using the non-fluoride controI denti- frice. Table 2 summarizes the mean equilibrium pla- ::í Equilibrium Study teau values obtained for each test dentifrice in both i The baseline salivar) fluoride concentration in- saliva and plaque. Both saliva and plaque fluoride creased mark edly during regular, repeated use of flu- values incrcased with increasing Na2FP03 content of
  4. 4. r l i [26 Duckworlh/Morg· !lI ~1; ~! ~ 12l the dentifrices. As reported previously [Duckworth tl ,,~ al., 1989], linear regression analysis of the individua;j plaque fluoride data gave a statistically significan; o °1 I correlation coefficient of 0.433 (p < 0.025; F test). 10 contrast to the plaque results, it can be seen from,! table 2 that the mean equilibrium saliva íluoride COr,. E 0.8 a, centration tended to plateau at high fluoride dose. LL " Nevertheless, regression analysis of the individual ~i :n data indicated a highly significant dose-respo-g, ) ~ 0.6 " lf) correlation (p < 0.001). Furthermore, all mean ,salival fluoride values for the Na2FP03 dentifrices were sigo t; , nificantly higher than the corresponding mean value I for the non-fluoride control dentifrice (p < 0.01; anat. ,I ysis of variance), and the saliva fluoride values for lhe i ------------,.-----------,,-----------, dentifrices containing 1,500 and 2,500 ug fluoride per .!I, o 50 100 150 gram were significantly higher than the values for the li Time, days dentifrice with a fluoride content of 1,000 llg/g I>,i Fig. 3. Me~n equilibriurn salivary fluoride concentration, mea- (p < 0.05; analysis ofvariance), ~ sured at least 18 h after last brushing, during daily use of Na2FPOJ dentifrices (bárs = 50). O = Placebo; À. = 1,000 ug F/g; i 1,500 ug F/g;. = 2,500 ug F/g. Discussion I The salivary fluoride c1earance studies have shoWn that.mo~e than one process is in~olv.ed in fluoride re.I., "I tention 10 the mouth after application of a f1uoride ~, . dentifrice. Figure 2 indicates that cIearance curves ~l were consistent with a two-compartrnent open pha-, i macokinetic model, This model assumes three firs], i order rate constants which correspond to processes t for the elimination of a therapeutic agent from one . (4) compartment and for the uptake of the agent to, and .: release from, a second compartment [Wagner, 1975]. t Following this model, a possible representation of I Gut E-f.{6[X.fL the fate of fluoride in the mouth during and after ap- i plication of a fluoride-containing dentifrice is given Fig. 4. The Iate lir fluoride during and after dentifrice applica- in figure 4. Five stages are identified: (1) during brush. tion. For further expi:üiatiaii Sei: Disctrssion, ing the dentifrice becomes mixed with saliva in the rnouth; (2) fluoride species are taken up by the oral f Table 2. Equilrbr1um oral fluoride conéentlâtiOrls during tlre tissues; (3) after 30-60 s a major fraction of the ap. ) use ofNa1FPOJ deritifrices (ntean ± SD; n •• 7) plíed fluoride is lost from the mouth when the bulk of the saliva/ dentifrice slurry is spat out and the mouth Na,FP03 Saliva fluoride Plaque fluoride is rinsed with water; (4) the remaining fluoride is (F, iJ.gl ,) umcl/! ng/rng wet weight mostJy lost from the mouth by swallowing or is taken o OA3±o-.05 1.46±0.27 up by the oral tissues, and (5) as the salivary f1uoride 1,000 Ct15±O.06 1.76 ± 0.55 concentration decreases with time, the release 01 fluo. 1.500 O,84±O.05 }, L93 ±O.57 ride frorn the oral tissues is increasingly favoured. 2,500 0.81 tO,09 . 2.36:1: 1.20 The above scheme is probably broadly applicabls to topically applied therapeutic agents and, for exam- Saliva values c6tiiktted by the bar are not signiflcaruly dif- ple, is similar to models considered for the oral dispo- ferenl. sition of antíplaque agents [Gilbert et aI., 1987; van t
  5. 5. rn liva F!uoride from Dentifrices 127:-.. ~ ----~t derOuderaa and Cummins, 1989]. For completeness, centrations which increased with the Na2FP03 COI1-II I lht: distribution of any ingested agent via the systemic tent of dentifrices for up to 2 h after application.t " I blood circulation should also be included [Ekstrand Qualitatively similar findings were also reported by1 c!al., 1986; van der Ouderaa and Cummins, 1989]. Finidori and Lamendin [1980]. Bruun et al, [1987] fit-1 The sequ~r fluoride uptake and release repre.- ted cIearance curves obtained during the first 30 min ,.t1~ stages 2 a nd 5 can be viewed as the storage after dentifrice application using the Weibull func- ~ase O(]1uoride (or monofluorophosphate) tion. The present analysis appears to be generally ap- ir;-anatural oral reserv()ir~ Thus, the initial rapid plicable for a longer time period, up to 6 h in thisI ! I j;!il in saliv-aryfluoride~centration IS most "i1<eTy work, and is also more informative about the mecha- clearance of fluoride frorn the mouth by swallowing nisms involved in oral fluoride retention. iísâ resilTt of Ifiecontiiiiious flow of saliva (stage 4). The present study has involved fluoride-containing T~d~tive y slow, clearance phase is be- dentifrices. However, it would be expected that the I~e dUe to fluo ri de, retained in the oral reser- mode! should be applicable to salivary fluoride clear- ~pred~antl~in dentifrice a lication, ance following the use of other topical fluoridé treat- ~sequently rel~~ed into the saliva (stage ments. For example, there have been a number of ) . studies of fluoride clearance after use of NaF rnouth- ."Although the above interpretation may be simplis- rinses [Aasenden et aI., 1968; Heintze and Petersson, tíc, the model clearly provides an excellent represen- 1979; Bruun et aI., 1982; Zero et aI., 1988; Duckworth tation of the observed salivary fluoride clearance and Jones, 1989b]. The last mentioned workers behaviour within the experimental error of the mea- showed that equation I could be applied to such clear- surernents. ln aIl robabilit the o eservo·· C_Q - ance curves. sists of a number of microreservoirs, e.g., plaque, the The two-phaseclearance behaviour observed here . ~es of gums, tongue, and cheeks, and stagna- is similar to the salivary clearance of the antiplaque tion zones between the teeth, under the tongue, and in agent tricIosan reported by Gilbert and Williams lhe buccaI sulcus. Recent in vitro work indicated that [1987]. These authors estimated the half-lives of the lhe soft tissues might be the major reservoir for fluo- first and second phases to be 27 and 145 min respec- rrde [Duckworth and Jones, 1989a], as has been sug- tively. The corresponding mean half-lives obtained ges ted for the antiplaque agent triclosan [Gilbert and here fo-;--fluoride are 8 and 195 min res ectively. Williarns 1987]. Some authors have postulated that SfeeOrly et a!. [1985] also found two-phase saliv~ry lhe orally retained fluoride is stored ln the form of cIearance curves for sucrose and glucose. However, it (alclUm fluoride or calcium-fluoride-like material should be noted that the initial phase described here ~n et a!., 1981; R611a, 1988]. most probably corresponds to the second phase de- The contribution to whole saliva fluoride from scribed by the above authors. This phase is also the ductal saliva after a single dentifrice application will unstimulated saliva cIearance phase for sugar mo- be smai1. We estimate [Duckworth et al., unpubl. ob- delled by Dawes [1983]. servatioh1 the arnount (lf íluoride ingested at the time The equilibrium baseline fluoride levels attained in of dentifdce application to be less than 10% of the ap- the above clearance studies were very low « 1 umol plied dose, •.e., <0.225 mg frorn 1.5 g of a dentifrice F/I); in qualitativo agreement with Duckworth et al. contaif}írig 1,500 !-lg F/g. Oliveby et al. [1989} ob- [1987] who noted that the natural f1uoríde content of served that the maximurn elevation of the fluoride the drinking water in this region is relatively low (1.4 . r concentration measured in unstimulated whole saliva umol/I), Of crucial importance for the oral fluoride - / -"- i/ 50 min after ingestion of I mg fluoride was approxi- reservoir concept, however, is the observation that the mately 0.8 urriol/I above the corresponding baseline baseline leve! itself was elevated during regular use of vaiue. Th:Ís elevation decreased to 0.24 urnol/I after nuoride dentifrices. 1n these studies fluoride ~ure- 120min. Thus the contribution to the data of figure 2 ments were made on samples of saliva and plaque col- is unlikely to be more than 0.2 and 0.05 umol/I at 50 lected approximately 18 h after a dentifrice applica- and 120 rnin respectively. tion. The elevatíon in saliva is unlikely to have been The salivary fluoride clearance behaviour ob- caused by systemic fluoride. Ingram and Morgan served here is similar to the results reported by Bruun [1987] found that the f1uoride concentration in pa- et aI. [1984] who foundelevated salivary fluoride con- rotid saliva was approximately 80% of the value in
  6. 6. I__________ . . . D_u_c_k_W.~ whole saliva from subjects who had used a non-fluo- becomes 01 key importance if it can be shown thar l~ride dentifrice regularly for 1 month. However, the observed low fluo ri de concentrations can maintain 11former concentration did not change after repeated protective effect against dental caries. This aspecj i"daily use of a topical mouthrinse which contained bethesu~ectofasubsequentpaper. • 1,000 ug F/g, unlike the whole-saliva fluoride value[Ingram and Morgan, unpubl. observationJ. The relationship between increasing plaque flu- Referencesoride content and increasing applied dose is similarto that previously observed for NaF mouthwashes Aasenden R, Brudevold F, Richardson 13:Clearance 01 Ouori~~[Duckworth et al., 1987J. Birkeland [1972J and Main- from the mouth after ropical treatment 01 lhe use of a Ouorid.waring [1976J also recorded increases in the plaque rnouthrinse, Arch Oral 13iol 1968; I3:625-636. . Birkeland JM: Fluoride content of dental plaque after brushin lluoride concentration after regular use of dentifrices with a fluoride denlifrice. Scand.J Dent Res 1972;80:80-81. !ê~taining 1,000 ll.g F/g, as NaF andNa2FPO,,;:;; Bruun C, Givskov H, Thylstrup A: Whole saliva fluoride aftttspectively, reI ative to non-fluoride controls. toothbrusbing with NaF and MFP dentifrices with different r The mean equilibrium saliva f1uoride -concentra- concentrations, Caries Res 1984:282-288.tions measured in the present dentifrice study are Bruun C, Larnbrou D, Larsen MJ, Fejerskov O, Thylstrup A: Fluo. ride in mixed human saliva after different topical fluoride lreai.lower than those reported in a previous mouthwash ments and possible relation to caries inhibition. Communitstudy [Duckworth et al., 1987]. This difference is con- Dent Oral EpidemioI1982;10:124-129. .sistent with the corresponding plaque f1uoride data. Bruun C, Qvist V, Thylstrup A: Effect of flavour and detergent 00Duckworth et al. [1989] suggested that the accumula- fluoride availability in whole saliva after use of NaF and MFPtion of lower levels of fluoride in p!aque during regu- dentifrices. Caries Res 1987;21 :427-434. Corpron RE, More FJ, Clark JW: In vivo remineralisation of artifi.lar dentifrice use than during regular mouthwash use cial enamel lesions by a fluoride dentifrice 01 mouthrinse.could have been because of either the different modes Caries Res 1986;20:48-55.of application 01 interactions of lluoride with other Dawes C: Avrnathematical model of salivar) c1earance of su arformulation components in the dentifrices. Either ar Irorn the oral cavity. Caries Res 1983; 17:321-334.both 01 these possibilities could be responsible for the Duckworth RM, Jones S: On the interaction between f1uorine spe. cies and oral soft tissue. J Dent Res I989a;68:560. lower equilibrium saliva fluoride concentrations Duckworth RM, Jorres S: On the relationship betwecn salivarfound in lhe current dentifrice study. fluoride c1earance and the rate of salivary Ilow, Caries Res The tendency of the saliva fluoride concentration 1989b;23:43 7-438. .during the equilibrium study to plateau at high ap- Duckworth RM, Morgan SN, Burchell CK: Fluoride in plaque foi. ~plied fluoride dose was not observed with the corre- lowing use 01 dentifrices containing sodium moncfluorophs., phate. J Dent Res 1989;68: 130-133,sponding plaque lluoride concentrations nor with the Duckworth RM, Morgan SN, Murray AM: Fluoride in saliva <Indsaliva lluoride concentration observed in the previous plaque following use of fluoride-containing mouthwashes. Jmouthwash study. The reason for this behaviour is Dent Res 1987;66:1730-1734.not understood. The fact that the clearance curve pa- Ekstrand J, Lagerlõf F, Oliveby A: Some aspects of the kinetics ofrarneters after single use of the dentifrices (by the f1uoride in saliva; in Leach SA, Edgar WM (eds): Factors Rela]. ing to Demineralisation and Remineralisation ofthe Teeth. Ox.same subjects) did not plateau at a high applied f1uo- ford, IRL Press, 1986, pp 91-98.ride concentration suggests that the oral fluoride res- Featherstone JDB, OReilly MM, Shariati M, Brugler S: Enhanc-.ervoir responsible fót the elevated baseline fluoride ment of rernineralisation in vitro and ín vivo; in Leach SA, Ed.values is dorninated by à different reservoir source gar WM (eds): Factors Relating to Demineralísatíon and Re.than during lhe second clearance phase. However, the mineralisation oftheTeeth. Oxford, IRL Press, 1986, pp 23-34. Fejerskov O, Thylstrup A, Larsen MJ: Rational use of Iluorides inspecific sources responsible for these elfects cannot caries prevention. A concept based on possible cariostaticpresently be identified from arnongst the possibilities mechanisms. Acta Odontol Scand 1981;39:241-249.listed earlier. Finidorí C, Lamendin H: Amount of fluorine in saliva after use of The above results dernonstrate that repeated use of various toothpastes. Chir Dent Fr 1980;50:43-48.dentifrices containing Na2FPOj provides sustained Gelhard TBFM, Arends J: Microradiography of in vivo reminera. Ielevated levels of nu€Yride in the mouth between daily lised lesions in human enamel. J Biol Buccale 1984;12:59-65. Gilbert RJ, Fraser SB, van der Ouderaa FJO: Oral disposition of brushings. Furtherrnore, for a short period after each triclosan (2,4,4 -trichJoro-2 -hydroxydiphenyl ether) deli vered brushing, the salivar) fluoride concentration is rel a- from a dentífrice. Caries Res 1987;21 :29-36. I; tively high. The growing body of oral f1uoride data Gilbert RJ, WilJiams PEO: The oral retention and antiplaque effi. t L
  7. 7. 1 ~Iuoride fro_m_D_e_Il_1i_fr_ic_e_s . 12_9..•.!lI C:lçy 01 triclosan in human volurucers. Br J Clin Pharrnncol Renson CE. Crielaers PJA, lbikunlc SAJ, et al: Changing patternselI,.1 !9~7: ~J:5 79-5~U. of oral health and implications Ior oral hcalih manpowcr. l. lnt1 G0(lfhuis J, Purdell-Lewis DJ: 0.25% and 0.4% amine fluoride gel Dent J 1985;35:235-251.! I I<lrweek ly ropical application. An in vivo study on human den- R611a G: On the role 01" calcium fluoride in the cariostatic mecha- tal enamel. Cáries Res 1986;20:458-464. nism offluoride. ACIGlOdontol Scand 1988;46:341·-345. Hcintze U, Petersson LG: Accumulation and clearanee of fluoride R6l1a G, 0gaard B: Reduction in caries incidence in Norway from in hurnan mixed saliva after different topical fluoride treat- 1970 to 1984 and some considerations concerning lhe reason for 11cnts.Swed Deru 11979;3:141-148. this phenomenon: in Frank RM, OHickey S (cds): Strategy for Ip~nllnGS, Morgan SN: Oral fluoride lcvels and ambient fluoride Dental Cáries Pre ention in European Countries According to . inwke. Cáries Res 1987:21: 179. Their Laws anel Regulations, Oxford, IRL. Preso, 1987. pp J0l"t L:lrscn M. Lambrou 1). Fejcrsk ov O. T<I(h05 B: A study on 145-·154. 3ccui11ulati,)n and release of looscly bound fluoridc on cnarnel. Schâfer F: Evaluarion 01" the aniicaries benefit 01" fluoridc iooth- earies Res 1981; 15:273-277. pastes using an enamel insert model. Caries Res 1989;23:81-86. de Kloet HJ, Exterkare RAM, Rempt HE. ten Cate JM: In vivo bo- Sreebny LM, Chatterjee R, Kleinberg I: Clearance of glueose and vine enamel rernineralisation and fluoride uptake frorn two sucrose from lhe saliva of human subjects. Arch Oral Biol dentifrices containing different fluoride concentrations. J Dent 1985;30:269-274. Res 1936;65:1410-1414. Stephen K W, Creanor SL, Russell n, Burchell CK, Huntington E, ~{ainW3ring Pl: Fluoride, calciurn and phosphorus concentrations Downie CFA: A 3-year oral health dose response study of so- · in pia que following the use of a sodium monofluorophosphate diurn monofluorophosphate dentifrices with and without zinc toothraste (SM FP) containing ca1cium glycerophosphate citrate: Anti-caries results. Community Dent Oral Epidemiol (CaGP). l I. J Dent Res 1976;55(speeial issue D):142. 1988; 16:321-325. 13rquardt DW: An algorithm for least-squares estimation of non- Wagner JG: Fundamentais of Clinical Pharmacokinetics. Wash- · linear pararneters, J Soe lnd Appl Math 1963: 11 :431-441. ington, Drug Intelligence Publications, 1975. Marthaler TM: Explanations for changing patterns of disease in Zero DT, Fu J, Espeland MA, Featherstone lDB: Comparison ar rhe western world; in Guggenheim B (ed): Cariology Today. Ba- fluoride concentrations in unstimulared whole saliva following ,:1. Karger. 1984. pp 13-23. use of a fluoride dentifrice and a fluoride rinsc, J Dcnt Rcs !e!lberg .lR, Castrovince LA, Rotsides ID: ln vivo remineralisa- 1988;67: 1257-1262. · tion by a monofluorophcsphate dentifrice as determined with a tl1in-section sandwieh rnethod. J DeI1l Res 1986;65: I078-1083. !eIlberg JR. Chornicki WG, Mallon DE, Castrovince LA: Rernin- · erali,ation in vivo of artificial caries lesions by a rnonof1uoro- phosphate dentifrice. Cáries Res 1985: 19: 126-135. Received: March 19, 1990 MlIrray JJ, Rugg-Gunn AJ: Fluorides in Cáries Prevention. Bristol, Accepted after revision: Septernber 15, 1990 Wright-PSG,1982 Olileby A, Lagerlõf F, Ekstrand J, Dawes C: Studies on fluoride R.M. Duckworth excretion in hi.rnan whole saliva and its relation to flow rate Unilever Dental Research 3nd plasma tluoride lcvels. Caries Res 1989;23:243-246. Unilevcr Research Port Sunlight Laborarory van der Ouderaa FJG, Cummins D: Delivery systems for agents in Quarry Road East supra- and sub-gingival pia que contro!. 1 Dent Res 1989;68 Bebington (speci:!I issue): 1617 -1624. Wirral, Merseyside L63 3JW (UK) - .. ~-
  8. 8. ri ( !f[v/iC6f!CÚ+ 17,4- Cdr.: tI-" 1); VU:9~ 1}O tn J r t.~VJ-I... .,,~ .Jo