This document summarizes fluoride metabolism and toxicity. It discusses the history of fluoride use and poisoning cases. Fluoride is toxic in large amounts but provides dental benefits in small, regular amounts. The document outlines fluoride absorption, distribution, and excretion in the body. Both acute and chronic fluoride toxicity are addressed. Acute toxicity can cause death, while chronic exposure can lead to dental and skeletal fluorosis depending on the amount consumed over time. The critical period for fluorosis development is during the maturation phase of tooth development.

1. FLUORIDE METABOLISM
AND
TOXICITY
DR. PRIYANKA SHARMA
III MDS
DEPARTMENT OF PUBLIC HEALTH DENTISTRY
JSSDCH

2. 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

3. 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.

4. • 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.

5. 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.

6. • 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.

7. 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.

8. • 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)

9. 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:

10. 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

11. FLUORIDE
METABOLISM

25. ACUTE TOXICITY
The 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

26. • 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.

27.  FACTORS AFFECTING
• Bioavailability
• Route of administration
• Age
• Rate of absorption
• Acid base balance

28. 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.

29. • 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.

30. • 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.

31. • 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.

32. • 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.

33. • 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.

34. • 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.

35. • 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

36. • 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

38. 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.
38

39. 39

40. INDIAN J DENT RESEARCH 20(3) 2009
40

41. 41

42. 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. 42

43. • 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
43

44. 44

45. 45

46. 46

47. 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.
47

48. • 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.
48

49. • 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).
49

50. • 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).
50

51. • 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). 51

52. • [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.
52

53. 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.
53

54. 54

55. • 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.
55

56. 56

57. TF (Thylstrup, Fejerskov) Classification:
• In this classification the enamel changes as
observed on the single tooth surface can be
arranged into 10 classes.
57

58. 58

59. 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 59

60. 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.
60

61. • 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.
61

62. • 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
62

63. • 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.

64. 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)
64

65. • 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.
65

66. 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. 66

67. 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
67

68. 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.
68

82. 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.

83.  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.

84. 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.

85. • 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).

86. “TOO MUCH OF GOOD THING SPOILS
EVERYTHING”