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METABOLISM OF FLUORIDE

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CONTENTS

Introduction The Element fluorine Fluoride in the Environment Sources of fluoride Metabolism of fluoride

Absorption of fluoride Distribution of fluoride

Excretion of fluoride

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INTRODUCTION

Dental caries is an ancient disease which has affected humans atleast from the time that the agriculture replaced hunting.

It’s often referred to as a disease of civilization due to the prevailing pattern of caries during 20th century: high prevalence in the developed countries, low prevalence in the developing countries.

Fluoride ranks as a primary influence in better oral health because it has demonstrated that caries was not inevitable.

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Due to its safety, efficacy and cost effectiveness in preventing caries the use of fluorides in various forms thus remains cornerstone of most caries prevention programs. In the past few years a better understanding of the mechanism of caries has led to an appreciation of the importance of fluoride in the remineralization.

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The Element Fluorine

Member of halogen family, atomic number-9, atomic weight-19.

The Federal Register of United States Food and Drug Administration describes fluorine as an essential nutrient.

Freely available in nature, but never in its elemental state: high reactivity.

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Natural source: Fluorspar (CaF2 mineral is found), Fluorapatite (Ca10(PO4)6F2 mineral is found).

Concentration varies: earth, fresh ground water, sea water

Dietary constituents: fish, tea Non-dietary: toothpaste, mouth rinses, etc.

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Combined chemically in the form of fluoride, fluorine is the seventh in order of frequency of occurrence of elements, representing about 0.06% to 0.09% of the earth’s crust.

In rock & soil fluorine may occur in combined form in a wide variety of minerals such as fluorspar [CaF2], Fluorapatite [Ca10(Po4)6F2] & Cryolite [Na3AlF6].

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The word fluorine is derived from Latin term ‘Fluore’ meaning to say ‘Flow'.

The WHO expert committee on trace elements has included fluorine as one among the 14 physiologically essential elements for the normal growth & development of human beings.

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Fluorspar is the principal fluoride containing mineral & the theoretical fluoride content is 48.5%.

Fluorapatite is a constituent of rock phosphate & has a theoretical fluoride content of only 38 g/Kg.

Cryolite is a relatively rare mineral that is an essential raw material in the aluminum industry & has a theoretical fluoride content of 545 g/Kg.

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Fluoride is widely distributed in the earth crust where it averages 300 ppm ,and constitutes about 0.07% of its weight .

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FLUORIDES IN THE BIOSPHERE

• The normal level of the fluorides in the plants is about 2-20 mg/g of dry weight.

• Leafy vegetables such as cabbages,lettuce and brussels ,sprouts contain about 11-26 mg of fluoride on a dry weight basis.

• A few species of plants actively accumulate high concentration of fluoride like tea plants,for which concentrations of several hundred ppm have been reported.

• The concentration of fluoride in various animal food stuffs is almost as same as plant food.

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FLUORIDE IN THE LITHOSPHERE

• Fluoride concentration is very high in highly ingenous rocks,alkali rocks in geothermal waters and hot springs and in volcanic gases and fumaroles.

• High concentraions seen in – igneous rocks Hot springs Volcanic gases.• Fluorides is widely distributed in the earth’s crust

about 300ppm

Fluoride content is also high in silicates.

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Fluorides in hydrosphere

Fluorides are present in trace quantities in all surfaces and under ground waters.

Concentration is negligible in rain water.

Concentration of fluoride in water varies not only from place to place but also within the same locality.

Surface water contains significant quantities of water at levels of 0.8-1.4mg/kg

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Fluorides in Atmosphere

• Ambient air fluoride in several industrialized areas of the world have been reported in literature.

• Ordinarily in large cities , 1 cubic meter of air on an average , contains less than 0.05 mg of fluoride but significantly high values have been reported.

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OCCURRENCE OF FLUORIDE IN FOOD

• Jowar,banana,potatoes also contain substantial quantities of fluorides.

• Certain plants of such as taro,yams and cassava constitute the staple diet of people in many tropical areas particularly in South America and in the pacific.

• The fluoride content of beverages especially in dry tea leaves is about 100-400 ppm fluoride depending on the brand.

• Sardines ,salmon ,mackarel and other fish contains about 20 ppm of fluoride on dry weight basis

• Fluoride is also present in the drug combinations like general anaesthetics.

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• Drugs containing fluorides are benzothiadiazines such as diuretics,fluorosteroids and phenethiazines.

• Its also present in fluorobutyrophenones such as tranquillizers,methoxyflurane,enflurane and halothane as anesthetics.

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Metabolism of fluoride

Absorption

Distribution

Elimination

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ABSORPTION

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Mechanism of fluoride absorption

Absorption is mainly through stomach ,or via intestine , lungs or

skin.

Passive in nature.

Occurs by simple diffusion.

Absorbed in the form of undissociated weak acid, HF.

Rapid absorption, appears in blood within 30-60 minutes and is

distributed within the body.

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Rate and degree

Fluoride ingested on fasting stomach the degree

of absorption is 100% with a glass of milk is 70%

with calcium rich diet it is 60%

Peak plasma in fasting is reached in 30 mins and

if taken 15 mins after meal the peak occurs after

1 hour.

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From ingested water and beverages

Absorption from ingested drinking water is almost

complete (86-97%).

Ingestion from other beverages :

- It is as complete as that from plain water

- Absorption from milk and tea has been studied

closely.

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Ingestion from milk

Ericsson (1958) found that at concentrations of 1 and 4 ppm

fluoride ,the absorption from milk is slower than from water

but the ultimate percentage absorbed is nearly the same.

Ingestion from tea

Tea is a rich natural source of fluoride.

Average fluoride content is around 100ppm

Fluoride in tea is less available than that in water.

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From ingested diet

It is well absorbed from poultry, fish and meat

which have high concentration of fluoride.

Soluble fluorides are readily absorbed.

Sodium fluoride in salt will be ingested with

meals so it is slightly reduced.

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Ingestion with fluoride preparation

The fluoride in NaF & aqueous solution of NaF /

SnF containing pills is absorbed almost completely.

( 100% )

Fluoride varnish remains on the tooth surface for

upto 12 hrs. Fluoride diffuse in saliva and is when

absorbed there is a modest increase plasma

concentration.

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Ingestion from fluorocompounds

Inorganic fluoride compounds like sodium

fluoride is more rapidly and completely absorbed

when compared to sodium monofluorophosphate.

Organic fluoride compounds like fluoroacetates

and fluorophosphates are readily absorbed

whereas fluorocarbons are not absorbed at all.

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Amount of fluoride absorbed from fluorocompounds

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Fluoride in blood plasma

Plasma is the biological fluid into which and from which

fluoride must pass for its distribution elsewhere in the

body and for its elimination from the body.

It is the central compartment.

Fluoride is present in ionic and non-ionic forms

Plasma fluoride level-1µM and increases with age

Total plasma fluoride

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Pharmacokinetics of fluoride

Two compartment model

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Maximum concentration is reached in 30-60 minutes

After initial rapid increase concentration declines for

the next several hours.

The calculated half life is within the range of 2-9 hours.

There are no additive effects with repeated doses of

fluoride.

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Plasma fluoride concentration versus time

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• Fluoride concentration in the plasma rise and fall according to

the pattern of fluoride intake.

• They are also influenced by the relative rates of bone

accretion and dissolution and by the renal clearance rate of

the ion.Accretion is a process where most of the fluoride is burried with in the mineral cryastallites during the

period of crystal growth

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DISTRIBUTION

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Distribution of fluorides

Plasma is the central compartment.

Fluoride exists in two general forms:

a) Ionic / inorganic / free fluoride

b) Non-ionic / bound fluoride

Fluoride concentration in plasma is twice as high

as that of cells.

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Distribution in saliva

Ranges from 0.01 ppm to 0.05 ppm

Peak concentration within one hour.

Unstimulated saliva contains more fluoride

than stimulated

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Distribution in milk

In the range of 0.02 to 0.05 ppm.

Fluoride in cow’s milk is found to be higher

than in human milk.

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Distribution in soft tissue

Depends on the rate of blood flow to the tissues

Steady-state tissue -to -plasma fluoride

concentration ratios fall between 0.4 and 0.9.

Notable exceptions to this range include the brain

and adipose tissue in which it is less than 0.2.

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Distribution in hard tissues

99% of all fluoride in the human body is found in

mineralized tissues.

The balance of fluoride in the body can be negative

or positive.

Presence of fluoride causes a decrease in the

carbonate and citrate concentration.

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Distribution in dental tissues

Preeruptive fluoride acquisition.

Preeruptive maturation phase prior to eruption.

Post eruptive maturation.

Enamel is 2,200-3,200ppm, dentine is 200-

300ppm and cementum is 4,500ppm.

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FLUORIDE AND TOOTH DEVELOPMENT

Fluoride is a nutrient essential to the formation of sound teeth and bones, as are calcium, phosphorus and other elements obtained from food and water

1. PRE-ERUPTIVE: MINERALIZATION STAGE Fluoride is deposited during the formation of

enamel, starting at the dentinoenamel junction, after the enamel matrix has been laid down by the ameloblasts

It is available to the developing teeth by way of the blood plasma to the tissues surrounding the tooth buds

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Effect of excess fluoride: The normal activity of the ameloblasts may be inhibited, and a defective enamel matrix can form. Dental fluorosis can result.

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2. PRE-ERUPTIVE: MATURATION STAGE After mineralization is complete and before eruption,

fluoride deposition continues in the surface of the enamel

Fluoride is taken up from the nutrient tissue fluid surrounding the tooth crown

Much more fluoride is acquired by the outer surface during this period than in the underlying layers of enamel during mineralization

Children who are exposed to fluoride for the first time within the two years prior to eruption have the greatest amount of fluoride acquired during this pre-eruptive stage

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3. POSTERUPTIVE After eruption and throughout the

lifespan of the teeth: Fluoride from the drinking water,

dentifrice, mouthrinses and other surface exposures acts to inhibit demineralization and enhance remineralization, thus inhibiting the initiation and progression of dental caries

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Fluoride in enamel

(Amount of fluoride in the outer enamel is 2200 -3200 ppm)

Developing enamel: During the early stages of development ,there is small but

detectable background level of fluorides and if relatively high concentrations of fluoride is administered in diet or drinking water ,the small crystallites in this region take up fluoride readily.

The enamel is porous and appears to absorb fluoride preferentially and a fluoride peak or atleast a zone of relatively high fluoride enamel is usually found just before the enamel begins to mineralize rapidly.

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Erupted enamel

Fluoride distribution is not uniform across the thickness of enamel.

Even in the incompletely mineralized state , the accumulation of fluoride by enamel seems largely restricted to the surface region and the fluoride concentration is therefore always relatively high at the enamel surface compared with the interior.

In newly erupted teeth the surface fluoride concentrations were found to be highest in the first formed enamel near the incisal edge and decreased steeply towards the more recently formed cervical region.

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Acquisition of fluoride by the enamel surface appears to continue at a perceptible rate as long as the tissue remains porous.

Fluoride interferes with the process of maturation thus prolonging the length of time during which enamel is porous and therefore will extend the period of rapid fluoride uptake.

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Fluoride in dentin

(Amount of fluoride in the dentin is 200-300 ppm)

The apatite crystallites are considerably smaller than those of enamel and their surface area and their capacity to take up fluoride is consequently much larger.

In the permanent teeth the average concentration of fluoride in dentin appear to increase upto the age of 40.

Fluoride concentration tends to be low in secondary dentin.

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The distribution pattern of fluoride in the primary dentition is complicated by the process of physiological resorption ,which occurs at the pulpal surface prior to exfoliation.

The fluoride concentration in the pulpal surface of deciduous dentin rises during the period of root formation and falls during the period of resorption.

The greatest rise and fall in fluoride concentration is found in the pulpal surface of multirooted teeth.

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Fluoride in cementum

(Amount of fluoride in the cementum is 4500 ppm)

The concentration of fluoride in cementum is higher than that of any skeletal or dental tissue.

Fluoride concentration generally decreases from surface to interior.

Total fluoride content in cementum increases with age.

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Distribution in plaque

Fluoride content in plaque ranges from 15-64

ppm .

The ionic fluoride activity of neutral plaque is

between 0.08 and 0.8ppm and is too low to

inhibit the metabolism of plaque bacteria.

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Distribution in the fetus

Placenta acts as a total barrier to the fluoride; others

have suggested that it is only partial.

Recent studies have shown that placenta is not in any

sense a barrier to the passage of fluoride.

Direct relationship between serum fluoride

concentration of mother and fetus.

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EXCRETION

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Major route of removal is by kidneys

Determinant of amount of fluoride excreted in urine

a) Glomerular filtration rate

b) Renal clearance of fluoride

c) Percentage of filtered fluoride reabsorbed.

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Urinary excretion

Hodge etal identified two groups of individuals :

1. Individuals whose normal intake is fairly constant

(steady state)- excrete 80-90% in the urine

2. Individuals receiving elevated quantities for short

periods.

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Excretion through faeces and milk

10% of daily excretion can be accounted for in faeces.

When diet contains insoluble fluoride compounds,

larger amounts are excreted through faeces.

There is limited transfer of fluoride from plasma to

breast milk but fluoride content is increased if the

amount ingested is increased.

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Excretion in sweat and saliva

At ambient temperatures and humidity upto 25% of

fluoride excreted appeared in sweat.

During excessive perspiring appreciable amounts are

lost through sweat.

A negligible fraction can be accounted for in the saliva.

Fluoride is completely diffusible in saliva and it may

be incorporated into dental calculus.

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REFERENCES

Fejerskov O, Ekstrand J, Burt BA, Fluorides in dentistry;2nd

edition,1996:Munksgard publishers,55-65.

Murray JJ, Rugg-Gunn AJ, Jenkins GN, Fluorides in caries

prevention;3rd edition,1999:Varghese Publishing house,262-272

Mellberg JR, Ripa LW, Fluorides in preventive dentistry;1st

edition,1983:Quintessence publishing co, 81-95.

Soben Peter, Preventive & Community Dentistry: 4th Edi,2009

Arya Publishing House,243-245

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