FLUORIDE METABOLISM AND

TOXICITYDR. PRIYANKA SHARMA

III MDS

DEPARTMENT OF PUBLIC HEALTH DENTISTRY

JSSDCH

CONTENTS• INTRODUCTION

• HISTORY

• EFFECT OF FLUORIDE

- THROUGH FLUORIDATED WATER AT VARIOUS LEVELS

- THROUGH VARIOUS MEDIA (SMITH AND HODGE 1959)

• METABOLISM

- INTRODUCTION

- ABSORPTION

- DISTRIBUTION

- ELIMINATION

• ACUTE TOXICITY

• CHRONIC TOXICITY

• CONCLUSION

• REFERENCES

INTRODUCTION

• Fluoride, well established as one of the most toxic elements known to humans when ingested in large doses.

• It is likely among the least understood medicines that primary care practitioners may encounter in terms of its chronic toxicology.

• Like every chemical there are safe limits for fluoride ingestion beyond which harmful effects occur.

• Acute ingestion of fluoride in large quantities may be followed by rapidly developing signs and symptoms which may result in death.

• When it is ingested in relatively small amounts during the period of tooth development, it might lead to dental fluorosis.

• When larger amounts are ingested over a period of years, changes in the quality and quantity of skeleton may occur i.e. skeletal fluorosis.

• In areas of the world where fluoride is naturally elevated in the drinking water, endemic fluorosis is relatively common.

HISTORY• During 19th and 20th century, sodium fluoride was used as a

pesticide.• Many cases of accidental and intentional fluoride

poisoning occurred.• Lidbech et al 1943, mass poisoning occurred at the Oregon

state hospital. NaF was mistaken for powdered milk. Appx 17 pounds of NaF was added to 10 gallons of egg. There were 263 cases of acute poisoning and47 terminated fatally.

• Alaska, 1992- 150 ppm F in water supply was present due

to miscalculations. Almost 300 people had nausea,

vomiting, abdominal pain, diarrhea and One death.

• We have to remember that prolonged use of fluoride at

recommended level does not produce harmful

physiological effects in humans.

DEFINITIONS

• Excessive ingestion of fluoride over short period of time produce acute toxicity

• Excessive ingestion of fluoride over long period of time produce chronic toxicity.

• W.H.O, 1963 has recommended optimum level of fluoride in drinking water as 0.5 to 1.0ppm

• The average daily intake of fluoride from all source recommended for adults is 2.0 to 2.2 mg and in children 5-14 years it is 1.02 mg which leads to plasma levels of 0.008 to 0.08 ppm. (Nikiforuk)

Effect of F ingestion through

fluoridated water at various levels• The commonly recognized effects of fluoride ingestion

through fluoridated water at various levels are given below:

Effect of fluoride through various media

(Smith and Hodge 1959)

Concentration of fluoride or dosage

Medium Effect

2ppm Air Injury to vegetation

1ppm Water Dental caries reduction

2ppm or more Water Mottled enamel

5ppm Urine No osteosclerosis

8ppm Water 10% osteosclerosis

20-80 mg/day or more Water or air Crippling fluorosis

50ppm Food or water Thyroid changes

100ppm Food or water Growth retardation

More than 125ppm Food or water Kidney changes

2.5 to 5 gm of F Acute dose Death

FLUORIDE METABOLISM

ACUTE TOXICITYThe acute lethal dose for an adult is suggested to be 32-64 mg F/kg, and in children it is 5mg F/kg.

• Certainly lethal dose (CLD):

Amount of drug likely to cause death.

Adult = 5-10 g NaF taken at one time or 32-64 mg F / Kg body weight

Children = 2.5 g of NaF

• Minimum lethal dose(MLD)/ Probable toxic dose(PTD)

Sufficient to cause severe toxicity and in the absence of medical treatment, can be lethal.

• Safety Tolerated Dose(1/4 CLD)

Maximum dose that can be given without toxicity

Adult = 1.25-2.5 g NaF or 8-16 mg F / Kg body weight

• It is always essential to know the fluoride concentrations in the dental products by the person who uses them.

• It is also important to know the amounts of fluoride that are contained in the unit packages, as well as the amounts involved during routine use.

• Many cases of acute toxicity have occurred because of the use of high doses of fluoride containing dental products, especially by the children.

FACTORS AFFECTING

• Bioavailability

• Route of administration

• Age

• Rate of absorption

• Acid base balance

SIGNS AND SYMPTOMS

• In nearly all cases of fluoride poisoning, the victims experience nausea, vomiting and abdominal pain within minutes after ingestion.

• Some non-specific symptoms may or may not be seen, such as excessive salivation, tearing, mucous discharge from the nose and mouth, diarrhoea, headache, cold wet skin or convulsions.

• As the epidose progresses, a generalized weakness, carpopedal spasms and tetany often develop.

• Immediate treatment should be aimed at reducing the amount of fluoride present for absorption in the GIT.

• This can be achieved by inducing vomiting, followed by oral administration of calcium containing solutions, large amounts of lime water or milk can be used.

• Administration of aluminium hydroxide gels should be exceptionally good for binding fluoride.

• Vomiting should not be induced if the victim has no gag reflex or while unconscious or convulsing because of the danger of aspiration.

• The victim should be immediately taken to the hospital.

• A cuffed endotracheal tube should be inserted, followed by gastric lavage with a solution containing calcium or activated charcoal.

• In the hospital, the treatment depends on the severity of signs and symptoms.

• If the patient is symptomatic, immediate attention should be given in establishing patent air way, intravenous line which should include sodium bicarbonate or ringer lactate solution to minimize the degree of acidosis and to elevate the urinary pH.

• Because of rapid elimination of fluoride in the urine, a subject surviving the first 24 hrs has a good prognosis.

• Monitoring and maintaining the cardiovascular circulation is also important.

• Blood samples should be taken hourly for the analysis of plasma fluoride concentration.

• Continuous evaluation of evidence for hyperkalemia and hypocalcemia through serum chemistry analyses.

• ECG monitoring and testing for muscle excitability may be required.

• The pulse may be thready or not detectable. • Blood pressure often falls to low levels. • Respiratory acidosis develops due to the

depression of respiratory centre. • Cardiac arrhythmias may develop in association

with the hypocalcemia and hyperkalemia. • Extreme disorientation or coma usually precedes

death which may occur within the first few hours after the fluoride exposure.

• Even if the patient shows signs of favorably responding to treatment, clinical monitoring should continue until the vital signs, serum chemistry profile and mental alertness are within normal ranges.

• Based on the concentrations, the following recommendations should be followed for mouth rinses, dentifrices, 0.4% stannous fluoride gels and tablets.

• They should not be used by young children without the supervision and presence of an adult.

• They should be kept out of reach of children.

Journal of Public Health Dentistry Vol. 57, No. 3, Summer 1997

• For high concentration fluoride formulations such as 1.23% APF gels, the following recommendations should be followed.

• They should be applied by dental professional only.• The patient should not be left unattended. • The quantities used and after the application, the

quantities left in the mouth should be minimized.

Journal of Public Health Dentistry Vol. 57, No. 3, Summer 1997

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CHRONIC TOXICITY• Fluoride, when ingested in small amounts for a longer

period produces dental fluorosis. • The severity of changes depends on the amount of fluoride

ingested. • Clinical features vary depending on the severity from

fine white lines in enamel to severely chalky, opaque enamel which breaks apart soon after tooth eruption.

• Really high concentration of fluoride for a long duration will cause skeletal fluorosis.

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INDIAN J DENT RESEARCH 20(3) 2009

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ETIOLOGY AND PATHOPHYSIOLOGY OF FLUOROSIS• Fluoride, when ingested during the formation and

maturation of tooth enamel, interferes with a number of cellular events because it inhibits various enzyme systems (DenBeston, et al, 2002), the G-protein complex (Matsuo, et al, 1998), and it removes and replaces proteins with enamel crystals (Aoba and Fejerskev, 2004).

• The severity of the defect appears to be proportional to the total fluoride consumed.

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• The condition nearly always occurs with symmetry, that is, teeth that developed at the same time are similarly affected.

• When fluoride exposure is early in life (age 1-3 years), only the anterior incisors and first molars are affected.

• When excess exposure occurs later, while the premolars, canines and second molars are developing, then sometimes these teeth are the only ones affected (Ishii and Suckling, 1991).

• Excessive fluoride intake from birth results in dental fluorosis in all the teeth

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THE CRITICAL PERIOD FOR FLUOROSIS DEVELOPMENT

• For years it was assumed that fluoride absorbed during the secretary phase of tooth development had the greatest effect on fluorosis, but more recent research with animals (Johnson and Bawden, 1987; Richards et al., 1986) and humans now suggests that the later maturation phase is more important.

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• Where fluorosis is found among human populations, observers have noted that teeth which mineralize later in life generally show more severe fluorotic disturbances than do those that mineralize earlier (Baelumet al., 1987; Larsenet al., 1985, 1987,1989).

• This finding is attributed to the older children's ingesting greater absolute amounts of fluoride in single dosages than do younger children, thus exacerbating the "spiking" effect of plasma fluoride.

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• The initial research reports that used the Fluorosis Risk Index (Pendrys and Katz, 1989) have permitted epidemiological identification of the maturation period as the critical stage of tooth development as far as fluorosis is concerned (Pendrys and Katz, 1989; Pendrys and Stamm, 1990).

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• On a larger scale, in 1978, reduction in the fluoride concentration of Hong Kong's drinking water from 1.0 mg/L to 0.7 mg/L allowed various birth cohorts to be studied so that the effect of this change could be evaluated.

• Not only did fluorosis diminish, but also the importance of the maturation stage in fluorosis development was clearly demonstrated (Evans, 1989).

• Evans concluded that the development of dental fluorosis may occur over a period of 16- 24 months, commencing from 12-32 months following enamel secretion (Evans, 1989).

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• The evidence thus suggests that the maturation phase of tooth development is more critical for fluorosis than is the earlier, secretary phase, though the relationship between quantity and timing of fluoride intake in both phases needs further definition.

• The research evidence suggests that the critical time for fluorosis development in anterior teeth may be the second or third year of life (Johnson and Bawden, 1987).

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• [McDonagh et al., 2000; NationalHealth and Medical Research Council, 2007].

• The development of dental fluorosis is influenced by the total fluoride ingestion from all sources, including toothpaste, during tooth development.

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CLASSIFICATION AND CLINICAL FEATURES: Dean’s Classification: • Dean in 1934, has classified dental fluorosis into six

categories according to the severity of condition. • Examination to be done under good sunlight facing the

window.• He also found that the severity of fluorosis was directly

related to the concentration of fluoride in the water.

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• Dean had found that majority of residents residing in communities where the fluoride levels are 1.2 ppm or less are normal, only mild levels of fluorosis are detected and no residents exhibit disfiguring brown spots or pitting.

• At approximately 2ppm F, moderate fluorosis is observed, while severe florosis occurs at approximately 3ppm F.

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TF (Thylstrup, Fejerskov) Classification:• In this classification the enamel changes as

observed on the single tooth surface can be arranged into 10 classes.

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FDI classification• It was called dental developmental index modified in 1989• Normal• Demarcated opacities• White/cream• Yellow/ brown

• Diffuse opacities• Lines, patches, confluent, staining or loss of enamel

• Hypoplasia• Pits 0r missing enamel

• Any other defects

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OTHER FEATURES• The tooth erupts with an intact enamel surface,

but the degree of subsurface porosity determines the subsequent post erutpive clinical features of that particular tooth.

• Thus, if the degree of porosity is so extensive at the time of eruption that the hypomineralized fluorotic enamel is covered only by a relatively thin, but well mineralized surface layer, the tooth will be very susceptible to mechanical trauma.

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• Pitting occurs shortly after eruption, often leading to more extensive surface destruction depending on the initial degree of hypomineralization.

• Fluorosis occurs symmetrically within the dental arches; the premolar is usually the most affected, followed by the second molar, maxillary incisor, canine, first molar and mandibular incisor.

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• Fluorosis is usually limited to the permanent dentition because of the modifying effect of the placenta on fluoride transfer to the fetus or shorter period of enamel formation.

• Chances of consumption of large quantities of fluoride is minimal

• Usually treatment is only symptomatic as the condition is irreversible.

• Esthetics is the major concern in anterior teeth.• In anterior teeth bleaching techniques or composite

veneers are considered.• Mottling in posterior teeth can lead to severe attrition and

pulpal exposure.• Early intervention with crown placement is always

advisable.

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SKELETAL FLUOROSIS• This is a crippling skeletal condition and it is a

major public health problem in the areas where fluoride levels are severely elevated (Ayoob and Gupta, 2006).

• Skeletal fluorosis remains an undiagnosed problem but there have been several obvious cases reported (Whyte, et al, 2005, Eichmiller, et al, 2005, Boyle and Chagnon, 1995)

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• When fluoride is ingested in larger amounts over a period of years, it might lead to skeletal fluorosis. • A more severe form is crippling skeletal

fluorosis. • Skeletal fluorosis occur approximately at a

water fluoride level of or above 8ppm.

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CLINICAL FEATURES• It is characterized by an increase in the radiographic

density of trabecular bone in the lumbar spine, pelvis and elsewhere in the body.

• An increase in the thickness of long bone cortices due to endosteal and periosteal apposition.

• In more advanced cases calcification of ligaments occurs, especially in the spine.

• Although fluorotic bone is sclerotic i.e., more than the normal, it is not as strong as the normal bone and spontaneous fractures are common.

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CLASSIFICATION • Based on the symptoms• Mild: Gen. bone and joint pains• Moderate: Pain, stiffness, rigidity and restricted

movement of spine and joints• Severe: along with moderate symptoms, flexion deformity

of spine, hips and knees, genu valgum, genu verum(bowing and rotational deformity of legs)- mostly seen in children

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EFFECT ON BONE• Oral sodium fluoride therapy has been widely

evaluated for treating osteoporosis. • A study of the daily treatment of osteoporosis

failed to show a decrease in fracture rate, inspite of the increase in bone mass.

• This is because the bone formed by fluoride treatment is more brittle than the normal bone.

CONCLUSION• When used appropriately fluoride is a safe and

effective agent that can be used to prevent dental caries.

• In Indian Senario to ensure maximum results fluoridation techniques should be used in combination.

• As majority of population reside in rural areas in india water fluoridation may not be appropriate technique .

• Fluoride dentrifices and mouth rinses can be advised for the general population.

RECOMMENDATION

• Parental supervision of brushing or mouth rinsing

• The use of small amounts of tooth paste

• The use of products with lower fluoride levels

• Teaching children not to swallow tooth paste or mouth rinse

• Strict adherence to current recommendation by professionals who prescribe fluoride dietary supplement.

American Academy of pediatric dentistry,1967, revised in 2014.

REFERENCES• Fejerskov, J. Ekstrand, Brian. Fluorides in dentistry. 2nd

edition. • Mellberg and Ripa. Fluorides in preventive dentistry. 1st

edition. • John Murray, Rugg. Fluorides in caries prevention. 3rd

edition. • Stephen HY Wei. Clinical uses of fluorides. 1st Edition. • Amrit Tewari. Fluorides and dental caries. 1st edition. • McDonald. Dentistry for the child and adolescent. 5th

edition. • Skinner’s. Science of dental materials. 10th edition.

• Hussain J and Sharma KC. Environmental Monitoring and Assessment.

March 2010, Volume 162, Issue 1, pp 1-14.

• Textbook of community Dentistry, TR Gururaja Rao. 2004 edi.

• Rajan et al 1987,1988, Use of fluoridated toothpaste - Blood fluoride

levels in children, International society of fluoride research.

• American Academy of pediatric dentistry,1967, revised in 2014.

Refernce manual , Vol 37 No.6.

• Lu,Y., Sun, Z.R. andWu,L.N.: Fluoride, 33(2): 74-78 (2000).

• Robinson, R.F., Griffith, J.R.,Wolowich,W.R. andNahata, M.C.:Vet. Hum. Toxicol., 44(2): 93-95 (2002).

“TOO MUCH OF GOOD THING SPOILS EVERYTHING”