Transcript Slide 1

DENT 5302 TOPICS IN DENTAL BIOCHEMISTRY
11 April 2007
Objectives:
• Acute and chronic fluoride toxicity
• Appropriate use of fluoride products
• Optimal and toxic level of fluoride intake
Outline
Historical perspective of fluoride toxicity and
current incidences
Toxic doses of fluoride from dental products
Guideline/recommendation for safe use
Symptoms of fluoride toxicity
Principle of emergency treatment
Chronic fluoride toxicity
Fluoride Toxicity
Excessive ingestion / short time:
Acute toxic effects
Gastric disturbance
Nausea, vomiting
Death
Excessive ingestion / long period during tooth
development:
Dental fluorosis
The effect of long term fluoride exposure on
bone is still controversial
Historical perspective of fluoride toxicity
Fluoride was used as a pesticide
Mistaken for powder milk, salt, baking soda, flour
1933-1955: 607 fatal cases in the US.
Pittsburgh 1940:
Salvation Army service center
Mistaken NaF for flour in pancake
40 poisoning cases & 12 deaths
Oregon 1943:
State hospital
Mistaken roach powder for powder milk
10 gallons of scrambled eggs + 17 lbs NaF
263 poisoning cases & 47 deaths
Lidbeck WL et al., JAMA1943;121:826-827.
Current incidences of F toxicity
US poison control centers
>20,000 reports/year of over-ingestion of fluoride
Sources of fluoride
Vitamins, dietary supplements, dental products (fluoridated
toothpastes or mouthwashes)
~ 90% are young children
~5% had minor symptom
~2% were treated in healthcare facility
a few cases with life-threatening symptoms and DEATH
Toxic Exposure Surveillance System Annual Report : F Toothpaste
American Association of Poison Control Centers
Year
No. of
Exposures
<6
6-19
>19
Treated
in Health
Care
Facility
Age
Outcome
None
Minor
Mod Major Death
2001
22,790
20,730
860
1,163
391
5,014
1,328
38
4
0
2002
24,087
21,965
954
1,129
411
4,852
1,218
40
1
1
2003
24,812
22,596
1,064
1,112
405
5,413
1,337
144
1
0
2004
24,180
21,890
1,026
1,213
440
5,187
1,272
42
0
0
2005
22,531
20,248
1,073
1,164
414
4,660
1,160
41
0
0
How much is too much?
‘Fatal dose’ or ‘Minimum lethal dose’ is not established for fluoride
Several variables affect the outcome
Exact doses were not precisely documented
Hodges and Smith (1965): ‘Certainly Lethal Dose’ (CLD)
Equivalent to LD100
Ingested dose that would be lethal to everyone if not
treated promptly
Based on case reports
CLD
= 5-10 g of NaF for adult 70 kg bodyweight
= 32-64 mg F/kg
Note: NaF has 45% fluoride by weight
Details of three deaths associated with the use of F-containing dental products
Body Wt
(kg)
Dose
(mg F/kg)
Not
reported
3.1 – 4.5*
Ingested ca. 100 F
tablets (0.5 mg); death
occurred 5 days later.
Dukes
(1980)
3 yr
12.5
16
Ingested ca. 200 F
tablets; vomited; death
occurred 7 hours later.
Eichler et
al. (1982)
3 yr
Not
reported
24 - 35*
Swallowed stannous
fluoride rinse solution;
vomited; death
occurred 3 hours later.
Church
(1976)
Age
27 mo.
Comment
Reference
* Calculated by use of the 3rd and 97th percentile values for three-year-old US boys
Whitford GM. J Dent Res 1990;69(Spec Iss):539-549.
How much is too much?
‘Probably Toxic Dose’ (PTD):
Threshold dose that could cause toxic signs and symptoms,
including death
Trigger immediate emergency treatment
More useful clinically
Not include chronic effect like fluorosis
***PTD = 5 mg F/kg***
PTD for 1-2 year old child, ~ 10 kg (22 lb) = 50 mg F
PTD for 5-6 year old child, ~ 20 kg (44 lb) = 100 mg F
PTD for adult, ~ 60 kg (130 lb) = 3000 mg F (3 g)
Some calculations of fluoride concentration
The most popular unit: ppm = part per million (wt/wt ; vol/vol)
Water with 1 ppm F = 1 g of F- per 106 g of water
Water density = 1 g/ml
Therefore, water with 1 ppm F = 1 g of F- per 106 ml of water
= 1 g of F- per 103 litre of water
= 1 mg of F- per 1 litre of water
Therefore, water with 1 ppm F = 1 mg/L
At higher concentration, usually use %
(F-containing products)
1 % = 10,000 ppm
0.1 % = 1,000 ppm
0.05 % =
500 ppm
Note that the concentrations can be either F-salt or F ions
The most common F-salt is NaF, which has 45 % F ions
(Na = 23; F = 19 ; MW NaF = 42 ; %F = 45 %)
e.g. A mouthrinse with 0.05 % NaF = 500 ppm NaF ~ 230 ppm F
How much is too much?
x 2 for 20-kg child (5-6 years old)
Concentration of
Product
Salt
Fluoride
%
Rinse*
NaF
%
ppm
= 50 mg F
Amount
containing PTD
for 10-kg child
(1-2 year old)
Typical
amount
used
Normal
size of
product
10 ml
18 oz (530 ml)
bottle
8 oz (~200 g)
tube
⅓ bottle
0.05
0.023
230
215 ml
* Prescription mouthrinses: 0.2 or 0.4%
Toothpaste
NaF
MFP
¼ tube
0.22
1.14
F supplement*
1 mg F
-
0.1
1000
50 g (~2 oz)
1g
0.15
1500
33 g
1g
-
-
1/6
tube
50 tablets
1/day
100 tablets
container
* 0.25, 0.5, 1 mg tablets depend on age
Adapt from: Monograph
2 out of 3 deaths of children caused by fluoride in dental products
were from the ingestion of fluoride tablets.
ADA recommends no more than 120 mg fluoride dispensed at once
Recommendations for parents:
Child-proof containers
Keep products out of reach of young children
Supervise children when brushing / rinsing
Do not swallow toothpaste / mouthrinse
PTD
Acute toxicity
Amount of fluoride ingested less than PTD
Chronic effect (fluorosis)
Possible acute toxicity in dental clinic: APF gel
1.23% fluoride in phosphoric acid
Upper and lower trays of 1.2-6 g/tray
Acidic condition (pH 3.5) enhances absorption
Because of acidity, a small volume can adversely affect the gastric
mucosa and lead to nausea or vomiting in some cases
ppm
Amount
containing PTD
for 10 kg child
(1-2 year old)
Typical
amount
used
12,300
4 ml
5 ml
Concentration of
Product
Salt
%
APF gel
2.72
Fluoride
%
1.23
Example: 5 g/tray x 2 trays = 10 g = 0.123 g F = 123 mg F
PTD for 1-2 year old child, ~ 10 kg (22 lb) = 50 mg F
> Double
PTD!!!
Symptoms of fluoride toxicity
Symptoms develop very fast, a few minutes after ingestion
Low Dosage
High Dosage
= low dosage symptom PLUS
Nausea
Vomiting
Abdominal pain
Hypocalcemia
&
Hyperkalemia
Convulsion
Spasm of the extremities
Generalized weakness
Diarrhea
Blood pressure drop
Hypersalivation
Cardiac arrhythmias
Tears
Respiratory acidosis
Discharge from nose and mouth
Extreme disorientation
Headache
Coma
Death
May occur within
the first few hours
Treatment of Fluoride Toxicity
Need immediate treatment
Reduce absorption
Induce vomiting immediately (providing no risk of aspiration)
Reduce bioavailability : 1% CaCl2 or calcium gluconate, milk
Transfer to hospital (as soon as possible)
Additional washing of stomach with lime water
IV fluid replacement
+ calcium gluconate : blood calcium level
+ sodium bicarbonate : urine flow rate & urinary pH
Other monitoring and supportive therapies
Generally, if death has not occurred in 1-2 days the prognosis is good.
Exception: 2 year-old boy died 5 days after ingesting 100 tablets 0.5 mg F
Can ingestion of fluoridated water cause acute toxicity?
PTD (Probably Toxic Dose) = 5 mg/kg
Optimal fluoridation 1 ppm = 1 mg/L
10 kg child has to drink 50 L of water with 1 ppm to reach PTD
Acute toxicity from water fluoridation
Accidental over-fluoridation of school or community water supplies
Most were relatively minor
Alaska, 1992
150 ppm F in water supply
Almost 300 people had nausea, vomiting, abdominal pain, diarrhea
One death
Chronic Fluoride Toxicity
Claim:
Long term ingestion of low level of fluoride (in water)
Allergic reaction, cancer, birth defects, genetic disorders, etc
Critical reviews on risk of chronic fluoride exposure
USPHS ad Hoc Committee on Fluoride, 1991
Long term ingestion of low levels of fluoride
(e.g., 5 ppm in water for years)
1. No detectable risks of cancer in humans
2. No indication that organ systems are affected
3. No association with birth defects, including Down’s syndrome
4. Skeletal fluorosis: relatively high F intake > 10 years
5. Osteoporosis & bone fracture: Benefit or Harmful or None ?
6. Dental fluorosis increase: Cosmetic or Toxic ?
Harvard bone cancer study
‘…an association between fluoride in drinking water during childhood
and the incidence of osteosarcoma...among males diagnosed less
than 20 years old, but no consistent association among females.’
Bassin EB, et al. Cancer Causes Control 2006;17:421-428
Positive association between fluoride and osteosarcoma in the first
set of cases (1989-1992) reported by Bassin et al.
The second set of cases (1993-2000) collected from the same
hospitals and similar methods of fluoride exposure does not
replicate the association found in the first set.
Fluoride level within the bone proximal to the lesion is not
associated with the excess risk of osteosarcoma.
Douglass CW, Joshipura K, Caution needed in fluoride and
osteosarcoma study. Cancer Causes Control 2006;17:481-482
Dosage of Fluoride Ingestion and Effects
Effect
Dosage
Duration
Optimal
0.05-0.07 mg/kg/day
-
Dental Fluorosis
> 0.10 mg/kg/day
Until age 6
Skeletal Fluorosis
0.15-0.33 mg/kg/day
10-20 years
Probable Toxic (PTD)
5 mg/kg
Acute
2 years old child (10 kg) + optimal water fluoridation (0.7-1.2 ppm)
Dietary fluoride intake ~ 0.5 mg (0.05 mg/kg/day).
ADA & American Academy of Pediatrics recommendation:
No fluoride supplement for children under 6 years old raised in
water fluoridation community.
Recommended references
1. Ekstrand J, Fejerskov O, Silverstone LM (Eds). Fluoride in Dentistry.
Copenhagen: Munksgaard 1988. Chapters 3 & 7.
2. Whitford GM. The Metabolism and Toxicity of Fluoride. 2nd ed.
Monographs in Oral Science Vol 16. Chapters VII & VIII.
3. Warren JJ, Levy SM. Systemic Fluoride. Sources, amounts, and effects
of ingestion. Dent Clin N Am 1999;43:695-711.
4. Bowen WH. Fluorosis. Is it really a problem? J Am Dent Assoc
2002;133: 1405-1407.
Harvard bone cancer study
Bassin EB, Wypij D, Davis RB, Mittleman MA. Age-specific fluoride exposure
in drinking water and osteosarcoma (United States). Cancer Causes Control
2006;17:421-428.
Douglass CW, Joshipura K, Caution needed in fluoride and osteosarcoma
study. Cancer Causes Control 2006;17:481-482.
Your patient calls: her 2 years old son ‘drank’ F-mouthrinse.
1. How much? A bottle is 18 oz (530 ml), she thinks he drank ¾ of it ~ 14 oz ~ 400 ml
2. What is the concentration? It should be in the ingredient: 0.05% NaF
3. Calculate the concentration of fluoride (e.g., in ppm): (It’s easier to do in steps)
1 % = 10,000 ppm ; 0.1 % = 1000 ppm ; 0.05 ppm = 500 ppm as NaF
NaF has ~ 45 % F ; therefore the concentration of F is ~ 230 ppm F
4. Then calculate the amount of fluoride
We know that 1 ppm = 1 mg/L, therefore 230 ppm = 230 mg F/L
The boy drank 400 ml, therefore he got (230 x 0.4) = 92 mg of fluoride
5. What is the boy’s weight? His mother says about 24 lb ~ 11 kg
Calculate PTD for the boy = 5 mg/kg x 11 kg = 55 mg
Therefore, the amount of mouthrinse he drank is almost double PTD!