Lecture 7 (11 April 07)
Fluoride Toxicity
As a dental practitioner, we should be aware fluoride is a hazardous substance. We have to make
sure that fluoride is used to enhance health with minimal adverse effects. Ingestion of fluoride
over a short time span can have acute toxic effects, ranging from gastric disturbance, nausea,
vomiting, or even death. Excessive ingestion of fluoride over a long period during tooth
development can cause dental fluorosis. The effect of long term fluoride exposure on bone is
still controversial.
Historical perspective and current incidences of fluoride toxicity
Fluoride was used as a pesticide, such as powder to kill cockroaches. Unfortunate events were
when fluoride was mistaken for powder milk, salt, or baking soda. From 1933-1955, 607 fatal
cases of fluoride toxicity were reported in the US. In 1940, NaF was added to pancakes at a
Salvation Army center in Pittsburgh. 40 persons were affected, and 12 died. In 1943, a hospital
in Oregon put 17 pound of NaF in 10 gallons of mixture for scrambled eggs. There were 263
poisoning cases with 47 deaths.
The current incidence of fluoride toxicity with fatal outcomes is much lower. Today’s fluoride
compounds are rarely used in pesticides. Still, more than 20,000 reports were filed each year to
US poison control centers concerning the possible overingestion of fluoride. Sources of fluoride
are vitamins, dietary supplements, and dental products. You may wonder who did that and how.
Nearly 90% are young children, and a lot of those cases involved fluoridated toothpastes or
mouthwashes. Current data shows that from those reports, a few percents were treated in
medical facility, and about 5% had minor symptoms. There were more than a few cases that
were life-threatening and even death.
Probably a lot of reports were parents who read the back of toothpaste tubes, which have
information for consumers to report any incidence. The topic of fluoride toxicity is of concern to
parents for the safety of their children. There are several ongoing discussions on the internet. As
a healthcare provider, you have to be aware of fluoride toxicity and be able to give an informed
advice.
Toxic doses of fluoride from dental products and guideline/recommendation for safe use
How much is too much? The fatal dose or minimum fatal dose is not established for fluoride
because there are several variables that can affect the outcome, and the exact doses involving
fluoride poisoning in humans are not precisely documented.
By reviewing case reports, Hodges and Smith concluded that a ‘Certainly Lethal Dose’ is 5-10 g
of NaF for adults with 70 kg bodyweight, equal to 70-140 mg NaF/kg or 32-64 mg F/kg. (Note
that NaF has ~45% F by weight) Certainly Lethal Dose is LD100, which is defined as a dose
that everyone who ingests that much fluoride will die if not treated promptly.
Three cases of fluoride-associated deaths of children were reported around 1980. The lethal
doses ranged from less than 5 mg F/kg to approximately 30 mg F/kg. The durations of the toxic
episodes were inversely related to the quantities of fluoride ingested. Clearly, there was
insufficient time of effective therapeutic intervention in the two cases where more than 15 mg
F/kg were ingested. These cases bring forward the more useful from clinical perspective: a
‘Probably Toxic Dose’ (PTD). PTD is the threshold dose that should trigger immediate
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emergency treatment (including hospitalization), even if it is only suspected that the PTD dose
has been ingested. PTD is 5 F/kg. For example, PTD for 1-2 year old child, ~ 10 kg (22 lb) is
50 mg F. PTD for 5-6 year old child, ~ 20 kg (44 lb) is 100 mg F, and PTD for adult, ~ 60 kg
(130 lb) is 3000 mg F (3 g).
Note that PTD has nothing to do with dose that can cause chronic effect like fluorosis, which is a
much lower dose but requires long term exposure.
Some calculations of fluoride concentration: The most popular unit for fluoride is ppm. ppm
means part per million (either weight by weight or volume by volume). For example, water with
1 ppm F means 1 g of F ions per 106 g of water. Water density is 1 g/ml. Therefore, water with
1 ppm F equals to 1 g of F ions per 106 ml of water, which is equivalent to 1 g of F ions per 103
litre of water, or 1 mg F per litre. At higher F concentration like those in F-containing dental
products, the unit is %. 1% is 10,000 ppm; 0.1 % is 1,000 ppm, and 0.05 % is 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 (atomic weight Na = 23; F = 19 ; molecular weight of NaF = 42 ;
therefore % F = 45 % by weight). For example, a mouthrinse contains 0.05 % NaF is equivalent
to 500 ppm NaF, or approximately 230 ppm F ions.
One day you may get a phone call from your patient, panicking that their child ate something that
should not be eaten. Can you tell them if it’s serious? The Probably Toxic Dose (PTD) for a 10
kg child, usually 1-2 years old, is 50 mg F. A child has to swallow 50 g (2 oz) of toothpastes (or
¼ tube) with 1000 ppmF, or 215 ml of 0.05 % F-mouthrinse (1/3 bottle), or 50 tablets of 1 mg Fsupplement to reach PTD. Some toothpastes are ‘extra-strength’ and contain 1500 ppmF.
Therefore the PTD for these high F toothpastes is only 33 mg (or 1/6 tube) for a 10-kg child.
Some prescription mouthrinses contain 0.2 or 0.4% F, 4 times higher than over-the-counter
products. Note also that there are 3 doses of F-supplement, 0.25, 0.5, and 1 mg tablets,
depending on the age of the child.
A normal dose of these products does not pose serious toxicity. For example, toothpaste is
usually applied in 1 g, mouthrinse 10 ml, and 1 a day for the tablet.
For an older child with higher weight, for example, a 5-6 years old child with 20 kg weight, just
multiply the PTD by a factor of 2.
2 out of 3 deaths of children caused by fluoride in dental preparations were from the ingestion of
fluoride tablets. ADA recommends no more than 120 mg fluoride be dispensed at one time.
Recommendations for parents: The mouthrinses and tablets should be in child-proof containers.
Parents should be educated to keep these products out of reach of young children and supervise
their children when brushing or rinsing not to swallow the products.
These numbers are PTD that can cause acute toxicity. Ingestion of fluoride in the lower amount
still can cause chronic effect, like fluorosis.
One exception to the amount of a normal use F product that can trigger acute toxicity is the
topical APF gel applied in dental practice. APF gel has 1.23% fluoride in phosphoric acid, and is
usually applied in upper and lower trays of 1.2-6 g/tray. PTD for 1.23% APF gel in 10-kg child
is 4 ml. So the amount used is twice the PTD level, serious toxicity can occur if a child swallows
only half of the applied gel. For 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. That’s more than double PTD!!! In
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addition, acidic condition enhances the absorption process. Because of the acidity, in some cases
even a small volume of APF gel can adversely affect the gastric mucosa and lead to nausea or
vomiting.
Symptoms of fluoride toxicity
Symptoms of fluoride toxicity develop very fast, a few minutes after ingestion. At relatively low
dosage as in case of APF gel, the subjects experience nausea, vomiting, and abdominal pain.
There may also be some non-specific symptoms like hypersalivation, tears, discharge from nose
and mouth, diarrhea, and headache.
Acute toxicity from high dosage of fluoride has these symptoms plus convulsion, spasm of the
extremities, and generalized weakness, which are signs of low plasma calcium (hypocalcemia)
and rising potassium level (hyperkalemia). Blood pressure often falls to a dangerous zone and
cardiac arrhythmias may develop. A respiratory acidosis develops as the respiratory center is
depressed. Extreme disorientation or coma usually precedes death, which may occur within the
first few hours. Prognosis is good if surviving the first 1-2 days.
Principle of emergency treatment
The immediate treatment of fluoride toxicity is to reduce the amount of fluoride available for
absorption at the gastrointestinal tract. Vomiting should be induced immediately providing no
risk of aspiration, such as, patient has no gag reflex or unconsciousness. Then follow by oral
administration of 1% calcium chloride or calcium gluconate to reduce bioavailability. If not
available, give as much milk as can be ingested.
The hospital emergency department should be informed and the patient should be transferred to
the hospital as soon as possible. The emergency team may insert endotracheal tube if the patient
is unconscious and do additional washing of stomach with lime water. IV fluid replacement
should include calcium gluconate to maintain blood calcium levels and sodium bicarbonate to
maintain urine flow rate and elevate urinary pH. Other monitoring and supportive therapies are
given by the medical team until the vital signs and serum chemistry are within normal ranges.
Generally, if death has not occurred during the first one or two days the prognosis is good.
Although there is a case that a 2 years old boy died five days after ingesting 100 tablets of 0.5
mg fluoride supplements.
Can ingestion of fluoridated water cause acute toxicity? At the optimal level of 1 ppm, a 10 kg
child has to drink 50 L of water to reach the PTD. However, there are incidents of acute toxicity
from accidental over-fluoridation of school or community water supplies. Most of the incidents
had relatively minor symptoms.
The most serious incident was in Alaska in 1992, when the fluoride level in the water supply was
150 ppm. Almost 300 people experienced nausea, vomiting, abdominal pain, and diarrhea.
There was one death in that accident.
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Chronic fluoride toxicity
There are several antifluoride groups, an example is this website. Most of them are against water
fluoridation. Since water fluoridation was introduced some 60 years ago, there were numerous
claims of harm from long term ingestion of low level of fluoride in water. The claims include
allergic reaction, cancer, birth defects, genetic disorders, for instance. Is it true? Of course the
answer is no, not those claims. But overingestion of fluoride can cause chronic fluoride toxicity.
Critical reviews on the risk of chronic fluoride exposure associated with fluoride concentration in
drinking water up to about 5 ppm state that:
1. No detectable risks that cancer in humans is associated with the consumption of optimally
fluoridated water.
2. No indication that organ systems are affected by chronic, low level fluoride exposure.
3. Fluoride exposure is not associated with birth defects, including Down’s syndrome.
4. Crippling skeletal fluorosis (the severe form of skeletal fluorosis) is not a problem in the US.
Skeletal fluorosis happens after a prolonged relatively high F intake for more than 10 years.
5. The beneficial or harmful effect of fluoride on osteoporosis & bone fracture is inconclusive.
6. The prevalence of dental fluorosis is higher than in 1940’s. There is disagreement whether
this is a cosmetic problem or toxic effect. (Dental fluorosis was covered in the previous lecture)
The possible chronic effect of fluoride is dental fluorosis, and in rare cases, skeletal fluorosis.
The association between bone cancer in humans with the consumption of optimally fluoridated
water is debatable at the moment because of this Harvard bone cancer study published last year.
Bassin et al reported 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 was found among females. Right after the publication, the Principal Investigator of
that study (who, somehow, is not the author in the paper) sent a letter to the editor that the
different findings are being prepared for publication. They also found a positive association
between fluoride and osteosarcoma in the first set of cases (1989-1992) reported by Bassin et al.
But 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. They also analyzed
fluoride content in the bone and found no association between fluoride level within the bone
proximal to the lesion and the excess risk of osteosarcoma.
This table combines dosage of fluoride ingestion for optimal effect, and those that can do harm
either in a chronic manner or acute toxicity. What we have to be careful about is dental fluorosis,
because the threshold is only slightly higher than the optimal level, and it happens in children
under 6 years old. Skeletal fluorosis can occur when one ingests more than double the optimal
fluoride level for longer than 10 years.
It has been calculated that the daily dietary fluoride intake of young children (about 2 years old,
10 kg) living in areas with water fluoridation in the range of 0.7 to 1.0 ppm, is approximately 0.5
mg (0.05 mg/kg/day). This is quite close to the threshold for fluorosis. Therefore, ADA and
American Academy of Pediatrics recommend the children under 6 years old raised in water
fluoridation communities (0.7 – 1.2 ppm) should receive no fluoride supplements.
There are also websites that support water fluoridation. One of them, is from a group of dentists.
The best one is probably the ADA website.
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