11/2/2022

College of Medical Science

Department of Medical Laboratory

Submitted to:
1. What is minimata bay tragedy
 Identify the cause
 Mechanism
 effect of this disease
Minamata Disease is a poisoning disease that nervous system, mainly central nervous system,
is damaged by methylmercury. It is established that the disease differs from inorganic mercury
poisoning which damages kidneys, etc., and also, it isn't confirmed that it damages organs other
than nervous system.
In the late 1950s Minamata Bay, Japan became contaminated with mercury from a nearby
factory manufacturing the chemical acetaldehyde (Chisso Corporation's chemical waste pipe).
The mercury was biotransformed by bacteria in the water into methylmercury, or organic
mercury, that bioaccumulated and biomagnified in the muscle of fish. First, local cats that ate
the fish began to stagger about and die. Then, the local population of people that depended on
fish were affected, particularly developing fetuses and children. Over two thousand people died,
and thousands more experienced crippling injuries. 

1.1 The Cause of the disease

The company responsible for the Minamata epidemic was the chemical company Chisso.
Chisso was a predominant company with advanced technologies in Japan at the time. In the
Minamata disease episode, methylmercury was generated as a byproduct in reaction chambers
for manufacturing acetaldehyde that was synthesized by a hydrolysis of acetylene using
mercury as a catalyst. Methylmercury, after discharging into the sea, accumulated in fish and
shellfish by the absorption through the gills or digestive tracts. Following the official
identification of the first patient in 1956, research teams were organized in Kumamoto University
School of Medicine and later in the Ministry of Health and Welfare (MHW). The University
research group identified the causative agent within the first three years. However, the
epidemiological findings were not effectively exploited to prevent the spread of the disease.
Early epidemiological studies in 1956 found 55 cases of the disease, which included 17 deaths.
These studies indicated that the disease was closely associated with the consumption of fish
and shellfish and suggested that it might be a kind of heavy metal poisoning. The factory waste
was
suspected as the source of the causative agent but it seemed difficult to prove it. Since the
ingestion of marine products caught in Minamata Bay apparently caused the disease, the
Kumamoto Prefecture government recommended not eating fish and shellfish of the bay in
1957, but did not actually prohibit the fishing or eating of them.
As new patients continued to be found during the summer of 1958, the Minamata fishermen’s
cooperative claimed compensation for damages of fishing operation in the hazardous sea area
and demanded immediate elucidation of the cause of the disease. In this period Chisso
intended to increase the production of acetaldehyde, for which there was much demand as a
raw material of octanol, a chemical used in polyvinyl chloride manufacturing. Engineers of the
company assumed that if there were any toxicity contained in the waste, it could be eliminated
by dilution with a large excess amount of seawater. Chisso changed the acetaldehyde drainage
channel from the waste outfall of Minamata Bay, where water tends to stay, to the mouth of
Minamata River in September 1958. However, the results differed from their expectations and
strengthened suspicions about the association between the factory waste and the cause of the
disease. In March of the following year, patients began to appear around the Minamata River
mouth area in addition to the Minamata Bay and neighboring areas. The areas in which patients
appeared expanded further around every costal region of the southern Yatsushiro Sea.

The research group of Kumamoto University presented, in July 1959, the organic mercury
hypothesis for the etiology of Minamata disease based on pathological and clinical findings and
on the fact that mercury was detected at extremely high concentrations in the sludge of
Minamata Bay with a maximum of 2,000 ppm at the waste outfall. Chisso officially argued that
1) the factory had been using inorganic, but not organic, mercury as a catalyst since the 1930s
without appearance of the disease, 2) Minamata disease had never been reported elsewhere in
neighboring chemical plants using mercury, a common chemical, 3) although alkylmercury
compounds are soluble in organic solvents, animal experiments using cats indicated that toxic
agent could not be extracted from poisonous fish or shellfish with the solvents and were found
to remain in insoluble fraction, and 4) the research group was unreliable, because it had been
presenting other hypotheses of manganese, selenium, and thallium to that point without any
success. However, the company had not mentioned at all several important facts, such as 1) the
possible formation of methylmercury during the course of the chemical reaction in the
synthesizing chamber containing inorganic mercury had been postulated, 2) the production of
acetaldehyde had increased substantially in the Minamata factory during the 1950s, 3) an
oxidizer of the synthesizing process, manganese dioxide, was replaced by ferric sulfide in 1951,
and 4) neurological signs resembling Minamata disease had been induced in the cats at the
Chisso laboratory after the ingestion of not only fish and shellfish caught in the Minamata Bay
but a diet mixed with the waste liquid obtained from the acetaldehyde process of the factory.
The oxidizer change is now considered to affect the yield of methylmercury in the reaction
chamber. Concerning the paradoxical findings on the extraction of methylmercury from
biological samples, it has since been found that methylmercury covalently binds to cysteine
residue of polypeptides in organisms (as mentioned below) and it cannot be extracted by
organic solvents without the hydrolysis of protein.
1.2 Mechanism to solve the Problem

Following the presentation of the organomercury theory by the University of Kumamoto, local
fishermen demanded that Chisso install a complete treatment system for plant effluent and
suspend operation until the installation of such a system. Meanwhile, patients of Minamata
Disease organized sit-ins in front of the main gate of the Chisso Minamata Plant, demanding
compensation.
The MITI gave a guidance to Chisso in October 1959 to install a plant effluent treatment system,
and Chisso completed the installation of a coagulation sedimentation system on December 19,
1959. With the reporting of the completion of the plant effluent treatment system by the mass
media, there was rising local expectation of the treatment of the effluent by this system.
However, it was later discovered that the system was not designed to remove mercury and was
useless for the removal of methylmercury compounds in the effluent.
Some movement was made in December 1959 regarding the issue of compensation. A
compensation agreement for fishermen was reached on December 25, 1959 between Chisso
and the Federation of Fishermen's Cooperatives in Kumamoto Prefecture with the help of the
Arbitration Board for Fisheries Disputes in the Shiranui Sea, members of which included the
Governor of Kumamoto Prefecture and the Mayor of Minamata City. The same Arbitration Board
also helped with the signing of the so-called consolation payment agreement between Chisso
and the Mutual Help Group of Households with Minamata Disease Patients on December 30,
1959. One clause of this agreement stated that recipients of this payment would not demand
further compensation even if Minamata Disease was found to be caused by effluent from the
Chisso Plant in the coming years.
The installation of the coagulation sedimentation system, fisheries compensation payment and
consolation payment to patients eased the intensity of the local dispute on Minamata Disease
by December 1959, and the problem of Minamata Disease ceased to be a major topic of social
concern without clarification of its cause. Although the research by the University of Kumamoto
to investigate the cause continued, hardly any progress was made regarding control or
prevention measures by the governments until the outbreak of the same disease in Niigata
Prefecture in 1965.
1.3. The Effect of the disease
Environmental pollution by toxic substances results in serious damage such as health damage
and destruction of the living environment. From the instance of Minamata Disease, Japan has
learned that an approach to prioritize economic goals without proper attention to the
environment causes serious problems including damage to health, and it is also not easy to
recover from it later on. From the economic standpoint, it is clear that such an approach are not
economically viable choice because the measures against this type of damage takes a large
amount of cost and a great deal of time in comparison with the cost for the case of taking
appropriate measures to prevent pollution.
The table below shows the results of the comparative analysis of the amount of damage caused
by Minamata Disease and the pollution control measures implemented in and around Minamata
Bay. This analysis was conducted in 1991 just before the UN Conference on Environment and
Development in Rio De Janeiro, Brazil. The amount of the damage is likely to be much larger if
it is calculated today.
Comparison of the Cost of Damage Caused by Minamata Disease in the Area Around
Minamata Bay to the Cost of Pollution Control and Preventive Measures (Unit: million Japanese
yen per year)

Cost for Pollution Control and Prevention Measures 123

Yearly average paid by Chisso Co.,Ltd., in the form of investments to control pollution
Total damage amount 12,631
Health damage
Yearly average of compensation benefits paid to patients under the 7,671
Compensation Agreement

Environmental pollution damage 4,271

Yearly average amount of expenditure for dredging work in Minamata Bay.

Fishery damage
Compensation paid to the fishery industry computed as equal redemption of 689
principal and interest prorated as yearly payment.
Source: "Pollution in Japan - Our Tragic Experiences", edited by Study Group for Global Environment and
Economics, 1991
Q.2. explain methemoglobinemia
 Identify the cause
 Mechanism or how disease occurr
 effect of this disease
2. What is Methemoglobinemia?
Methemoglobinemia occurs when red blood cells (RBCs) contain methemoglobin at levels higher than
1%. Methemoglobin results from the presence of iron in the oxidized ferric form (Fe 3+) instead of the
usual reduced ferrous form (Fe2+). This results in a decreased availability of oxygen to the tissues. This
condition can be congenital or acquired. 

Symptoms are proportional to the methemoglobin level. At levels up to 20%, changes can occur in the
color of blood (see the image below) and skin. As levels rise above 20%, neurologic and cardiac
symptoms arise as a consequence of hypoxia. Levels higher than 70% are usually fatal.

Note chocolate brown color of methemoglobinemia. In tubes 1 and 2, methemoglobin fraction is

70%; in tube 3, 20%; and in tube 4, normal.

With methemoglobinemia, the hemoglobin can carry oxygen, but is not able to release it effectively to
body tissues.

The reduction in the oxygen-carrying capacity of hemoglobin (Hb) in methemoglobinemia patients is due
to the conversion of some or all of the four iron species being reduced from the ferrous [Fe2+] state to
the oxidized ferric [Fe3+] state.

When the iron molecules of Hb are in the oxidized state, they are unable to bind and transport oxygen
and carbon dioxide, which can lead to a myriad of health complications.

The biochemistry behind the conversion of Hb into methemoglobin (MHb) can be better understood by
reviewing oxidation/reduction reactions. Whereas oxidation involves the removal of electrons from a
substrate, the reduction occurs when electrons have been transferred to the substrate.
Since oxidation and reduction reactions always occur together, this combination of reactions is often
referred to as “redox” reactions. As Hb is oxidized to MHb, inevitably, oxidation is also occurring in other
locations throughout the cell, thereby increasing the likelihood that other cellular enzymes and
organelles are damaged.

2.1 What is the cause?

Although methemoglobinemia most commonly refers to a condition that arises following exposure to an
oxidizing chemical, it can also arise as a result of genetic, chemical, dietary, or even idiopathic etiologies.

Genetic defect
Hereditary methemoglobinemia is a rare recessively inherited disorder due to deficiency of an enzyme,
called reduced nicotinamide adenine dinucleotide (NADH) cytochrome b5 reductase. Normal
erythrocytes are well endowed with a system to convert useless methemoglobin to functional
hemoglobin. The major mechanism for this reductive capacity resides in the soluble NADH
cytochrome b5 reductase. The gene regulating the synthesis of cytochrome b5 reductase has been
localized to chromosome 22q13qter, and a number of mutations have been identified. 1,2 Hereditary
methemoglobinemia due to NADH cytochrome b5 reductase deficiency is classified into 2 types—
erythrocyte (type I) and generalized (type II).

In the type I form, the soluble form of the enzyme is deficient only in erythrocytes, and cyanosis is the
only symptom.3 Type II hereditary methemoglobinemia is due to deficiency of the membrane-bound
form of the enzyme, which is located in the outer mitochondrial membrane and the endoplasmic
reticulum of somatic cells. Type II hereditary methemoglobinemia is a rare disease characterized by
deficiency of the enzyme in all tissues and manifesting with severe developmental abnormalities, severe
mental retardation, and neurologic impairment, which often lead to premature death. 4 Heterozygotes
with NADH cytochrome b5 reductase deficiency do not usually manifest signs of methemoglobinemia.
However, under the stress of oxidant drugs, severe cyanosis may develop because of
methemoglobinemia. Neurologic abnormalities do not respond to methylene blue therapy.

Exposure to drugs or toxins

The most common cause of methemoglobinemia, as in this clinical case, is ingestion of or exposure of
skin or mucous membranes to oxidizing agents (see box). Some of these oxidize hemoglobin directly to
form methemoglobin; others do it indirectly by reducing free oxygen to the free radical O 2-, which in turn
oxidizes hemoglobin to methemoglobin. Outbreaks of methemoglobinemia have occurred due to nitrite
poisoning from water contamination.5

Large amounts of nitric oxide are released in patients with sepsis. Nitric oxide is converted to
methemoglobin and nitrate. It has been reported that methemoglobin levels are significantly higher in
patients with sepsis than in nonseptic patients. 6

Methemoglobinemia has been reported in young infants (<6 months) in whom severe metabolic acidosis
develops from diarrhea and dehydration. 7 Young infants may be particularly susceptible to this
complication because of their low stomach acid production, large number of nitrite-reducing bacteria,
and the relatively easy oxidation of fetal hemoglobin. Small infants have lower erythrocyte levels of
cytochrome b reductase.8 Higher intestinal pH of infants may promote the growth of gram-negative
organisms that convert dietary nitrates to nitrites.

Idiopathic
The second most common cause of MHb is idiopathic and related to systemic acidosis, which will often
occur only in young infants younger than 6 months. In these patients, methemoglobinemia will occur
secondarily to diarrhea and/or dehydration.

Some factors that increase the susceptibility of small infants to methemoglobinemia include red blood
cell (RBC) levels that are low in cytochrome-b5 reductase (CYB5R), as well as more easily oxidized Hb.
Since infants often have higher pH levels within their gastrointestinal tract, there is greater support for
the production of gram-negative that convert dietary nitrates into nitrites, which are potent MHb
inducers.

Dietary
The ingestion of water that contains high levels of nitrates, which is more likely to occur in rural areas
where fertilizer runoff can enter public water supplies, can also lead to methemoglobinemia.

Acquired

Methemoglobinemia may be acquired. Classical drug causes of methemoglobinaemia include

various antibiotics (trimethoprim, sulfonamides, and dapsone), local
anesthetics (especially articaine, benzocaine, prilocaine, and lidocaine),
and aniline dyes, metoclopramide, rasburicase, umbellulone, chlorates, bromates, and nitrites. Nitrates
are suspected to cause methemoglobinemia.

In otherwise healthy individuals, the protective enzyme systems normally present in red blood cells
rapidly reduce the methemoglobin back to hemoglobin and hence maintain methemoglobin levels at
less than one percent of the total hemoglobin concentration. Exposure to exogenous oxidizing drugs and
their metabolites (such as benzocaine, dapsone, and nitrates) may lead to an increase of up to a
thousandfold of the methemoglobin formation rate, overwhelming the protective enzyme systems and
acutely increasing methemoglobin levels.

Infants under 6 months of age have lower levels of a key methemoglobin reduction enzyme ( NADH-
cytochrome b5 reductase) in their red blood cells. This results in a major risk of methemoglobinemia
caused by nitrates ingested in drinking water, dehydration (usually caused by gastroenteritis with
diarrhea), sepsis, or topical anesthetics containing benzocaine or prilocaine. Nitrates used in agricultural
fertilizers may leak into the ground and may contaminate well water. The current EPA standard of 10
ppm nitrate-nitrogen for drinking water is specifically set to protect infants. Benzocaine applied to the
gums or throat (as commonly used in baby teething gels, or sore throat lozenges) can cause
methemoglobinemia.

Pathophysiology
The affinity for oxygen of ferric iron is impaired. The binding of oxygen to methemoglobin results in
an increased affinity for oxygen in the remaining heme sites that are in ferrous state within the same
tetrameric hemoglobin unit. This leads to an overall reduced ability of the red blood cell to release
oxygen to tissues, with the associated oxygen–hemoglobin dissociation curve therefore shifted to the
left. When methemoglobin concentration is elevated in red blood cells, tissue hypoxia may occur.
2.2 Mechanisms

Initial Management

Early clinical recognition of methemoglobinemia is paramount, as patients often have only vague,
nonspecific complaints, especially in the initial phase. High levels of methemoglobinemia can be life-
threatening and necessitate emergency therapy. Patients with chronic mild increases in methemoglobin
level may be completely asymptomatic and require no specific therapy (provided that they have no
evidence of end-organ damage).

Once the diagnosis of methemoglobinemia has been confirmed and appropriate management has been
initiated, the underlying etiology should be sought. In acquired methemoglobinemia, if the toxin or drug
is not known from the history, it may be identified by obtaining blood levels, performing gastric lavage,
or both. In asymptomatic patients with low levels of methemoglobin, monitoring serial serum levels may
be all that is necessary. The levels normalize over time unless recurrent or chronic exposure to the
offending agent occurs.

Treatment is advisable for patients with acute exposure to an oxidizing agent who have methemoglobin
levels of 20% or higher. Patients with significant comorbidities (eg, coronary artery disease [CAD] or
anemia) may require therapeutic intervention at lower methemoglobin levels (eg, 10%), especially if
end-organ dysfunction (eg, cardiac ischemia) is present.

If methemoglobinemia is the result of toxin exposure, then removal of this toxin is imperative. Further
ingestion or administration of the drug or chemical should be avoided. If the substance is still present on
the skin or clothing, the clothing should be removed and the skin washed thoroughly. These patients
may be unstable and should be cared for in a closely monitored situation, with oxygen supplementation
provided as needed.

Pharmacologic Therapy, Exchange Transfusion, and Hyperbaric Oxygen

Methylene blue is the primary emergency treatment for documented symptomatic
methemoglobinemia. It is given in a dose of 1-2 mg/kg (up to a total of 50 mg in adults, adolescents, and
older children) as a 1% solution in IV saline over 3-5 minutes. Administration may be repeated at 1
mg/kg every 30 minutes as necessary to control symptoms. Methylene blue is itself an oxidant at doses
greater than 7 mg/kg and thus may cause methemoglobinemia in susceptible patients; hence, careful
administration is essential.

Methylene blue is contraindicated in patients with G6PD deficiency. Because it requires G6PD to work, it
is ineffective in G6PD-deficient patients with methemoglobinemia. Additionally, methylene blue
administration may cause hemolysis in these patients.

Methylene blue is also not effective in patients with hemoglobin M (Hb M). Other conditions in which
methylene blue may be ineffective or even deleterious include nicotinamide adenine dinucleotide
phosphate (NADPH) methemoglobin reductase (ie, diaphorase II) deficiency and sulfhemoglobinemia.

Methylene blue is listed as a category X teratogen. Intravenous ascorbic acid appears to be a potential

alternative to methylene blue in in pregnant patients with acute methemoglobinemia. However, given
that the data on the teratogenicity of methylene blue are mostly related to intra-amniotic or intra-
uterine administration, it is possible that in life-threatening cases of methemoglobinemia during
pregnancy, the benefits of methylene blue may outweigh the risk. [68]

The US Food and Drug Administration (FDA) warns against using methylene blue concurrently with
serotonergic psychiatric drugs, unless such usage is indicated for life-threatening or urgent conditions.
Methylene blue may increase central nervous system (CNS) serotonin levels as a result of monoamine
oxidase (MAO)-A inhibition, thus increasing the risk of serotonin syndrome. [69]

Exchange transfusion (which replaces abnormal hemoglobin with normal hemoglobin) may be
considered for G6PD-deficient patients who are severely symptomatic or unresponsive to methylene
blue. Patients who are on long-acting medication (eg, dapsone) may have initial treatment success with
subsequent relapse of symptoms. Gastric lavage followed by charcoal administration may decrease this
prolonged drug effect. These patients should be monitored closely and retreated with methylene blue as
necessary.

Hyperbaric oxygen treatment is another option for situations where methylene blue therapy is
ineffective or contraindicated. This approach permits tissue oxygenation to occur through oxygen
dissolved in plasma, rather than through hemoglobin-bound oxygen.

Infants with methemoglobinemia due to metabolic acidosis should be treated with IV hydration and
bicarbonate to reverse the acidosis. The NADPH-dependent methemoglobin reductase enzyme system
requires glucose for the clearance of methemoglobin. Therefore, IV hydration with dextrose 5% in water
(D5W) is often effective.

Patients with mild chronic methemoglobinemia due to enzyme deficiencies may be treated with oral
medications in an attempt to decrease cyanosis. These medications include methylene blue, ascorbic
acid, and riboflavin. The methylene blue dosage in this setting is 100-300 mg/day, which may turn the
urine blue in color. The ascorbic acid dosage is 200-500 mg/day; unfortunately, long-term oral ascorbic
acid therapy can cause the formation of sodium oxalate stones. The riboflavin dosage is 20 mg/day.

Cimetidine can be used in dapsone-induced methemoglobinemia to prevent further formation of its

metabolite. N-acetylcysteine has been shown to reduce methemoglobin in some studies but is not
currently an approved treatment for methemoglobinemia.

No pharmacologic treatment exists for hereditary forms of methemoglobinemia.

Diet and Activity

Rarely, the patient’s diet may include a substance that is the source of the methemoglobinemia. Well
water contamination with inorganic nitrates can be a particular problem with infants whose formula is
prepared with this water. Methemoglobinemia due to the ingestion of homemade fennel puree has
been reported in infants. Some vegetables (eg, beets, spinach, carrots, borage, and chard) are high in
nitrite or nitrate content and may have to be avoided by susceptible patients. [70]

Curcumin, the main curcuminoid in turmeric, has been shown experimentally to reduce
methemoglobinemia in rats treated with dapsone. [71]

No change in activity is indicated.

2.3 The effect of methemoglobinemia

The effect of methemoglobinemia include:

 headache
 shortness of breath
 nausea
 rapid heart rate
 fatigue and lethargy
 confusion or stupor
 loss of consciousness

People with severe methemoglobinemia (methemoglobin level above 50%) may exhibit seizures, coma,
and death (level above 70%).Healthy people may not have many symptoms with methemoglobin levels
below 15%. However, patients with co-morbidities such as anemia, cardiovascular disease, lung
disease, sepsis, or presence of other abnormal hemoglobin species (e.g. carboxyhemoglobin,
sulfhemoglobin or sickle hemoglobin) may experience moderate to severe symptoms at much lower
levels (as low as 5–8%).
Q. 3 explain health impact of excess or shortage of fluoride in water

3.1 Shortage of fluoride in water intake

 Adequate intake of fluoride has a beneficial effect on oral health in both children and
adults. Fluoride prevents caries by several different actions. When present in saliva and
dental plaque constantly and at low concentrations, fluoride delays the demineralization
and hastens the remineralization of tooth enamel lesions. Fluoride also interferes with
glycolysis, the process by which cariogenic bacteria metabolize sugars to produce acid.
In addition, fluoride has a bactericidal action on cariogenic and other bacteria. Finally,
when fluoride is ingested during the period of tooth development, it makes the enamel
more resistant to later acid attacks and subsequent development of caries.
 Reduce the incidence of dental caries by:
 fluoridating low-fluoride drinking-water where possible, as well as considering
alternatives, such as salt or milk fluoridation;
 developing effective and affordable fluoridated toothpastes for use in developing
countries;
 promoting optimal oral hygiene, based on the use of effective fluoridated toothpaste;
guidance on the amount of fluoridated toothpaste to be used and the concentration of
fluoride present in the toothpaste should take into consideration the age of the user
(especially for children) and the exposure to other sources of fluoride in the
community;
 supporting the use of silver diamine fluoride and atraumatic restoration treatment,
and other minimally invasive techniques, using glass ionomer cement to stabilize
caries lesions;
 Water fluoridation protects teeth in two main ways—by preventing the development of caries
through ingestion of drinking water during the tooth-forming years and through direct contact
of fluoride with teeth throughout life.
 A 2015 Cochrane review included 20 prospective observational studies (most conducted before
1975). The results showed that water fluoridation reduces the risk of decay and fillings, as well
as of premature loss of primary (baby) teeth, by 35% and loss of permanent (adult) teeth by 26%
in children receiving fluoridated water in comparison with children receiving unfluoridated
water. Fluoridation also increases the number of children with no decay in their baby teeth by
15% and the number of children with no decay in their permanent teeth by 14%. The authors
concluded that water fluoridation is effective for reducing dental caries rates in both primary
and permanent teeth in children. However, the reviewers were unable to assess the
effectiveness of water fluoridation for preventing caries in adults because no evidence met the
review’s inclusion criteria (which required studies to include at least two groups, one receiving
fluoridated water and one receiving unfluoridated water).
Table 3: Expert Panel Recommendations for Fluoride Supplementation in Children

Source Age Range Recommendation

USPSTF 6 months • Fluoride supplement (dose not specified) for children whose
and older water supply contains little or no fluoride*

American Dental 6 months to • Fluoride supplement (0.25 mg/day) for children whose water
Association** 3 years supply contains less than 0.3 ppm (0.3 mg/L) fluoride

3–6 years • Fluoride supplement (0.5 mg/day) for children whose water
supply contains less than 0.3 ppm (0.3 mg/L) fluoride
• Fluoride supplement (0.25 mg/day) for children whose water
supply contains 0.3 to 0.6 ppm (0.3 to 0.6 mg/L) fluoride

6–16 years • Fluoride supplement (1 mg/day) for children whose water

supply contains less than 0.3 ppm (0.3 mg/L) fluoride
• Fluoride supplement (0.5 mg/day) for children whose water
supply contains 0.3 to 0.6 ppm (0.3 to 0.6 mg/L) fluoride

pregnant women: Like other nutrients, fluoride is transferred from a pregnant woman to her fetus, so a
few studies have evaluated the use of fluoride supplements by pregnant women to prevent dental
caries in their children.

Safe and effective. For more than 70 years, the best available scientific evidence consistently has
indicated that community water fluoridation is safe and effective.

Saves money. When it comes to the cost of treating dental disease, everyone pays. Not just those who
need treatment, but the entire community – through higher health insurance premiums and higher
taxes. The average lifetime cost per person to fluoridate a water supply is less than the cost of one
dental filling.
It’s natural. Fluoride is naturally present in groundwater and the oceans. Water fluoridation is the
adjustment of fluoride to a recommended level for preventing tooth decay. It’s similar to fortifying other
foods and beverages, like fortifying salt with iodine, milk with vitamin D, orange juice with calcium and
bread with folic acid.

3.2 Excessive fluoride Intake in water

Excessive exposure to fluoride has been linked to a number of health issues.

 High fluoride intake can induce toxic effects by binding with calcium and interfering
with the activity of proteolytic and glycolytic enzymes.
 Ingested fluoride reacts with gastric acid to produce hydrofluoric acid in the stomach.
Thus, acute exposure to high concentrations of the most soluble fluoride compounds
results in immediate effects, including abdominal pain, excessive saliva, nausea and
vomiting. Seizures and muscle spasms may also occur. Death due to respiratory
paralysis is a possibility.
 The acute effects of inhalation of hydrogen fluoride are severe irritation of the
respiratory tract, with asthma-like reactions and pulmonary oedema. Severe burns or
damage may result from skin or eye contact. Inhalation, ingestion or dermal exposure
can be fatal.
 Repeated or prolonged exposure via inhalation of aluminum fluoride, primarily in
occupational settings, may cause asthma.

The main effect of long-term ingestion or inhalation of high concentrations of fluoride

is fluorosis:
 Enamel fluorosis can develop only in children, as it results from intake of high
levels of fluoride during the period of tooth development. It is characterized by the
appearance of white areas in the enamel and in this form is considered an aesthetic
issue. In the more severe form, reduced mineralization of the enamel results in
stained and pitted teeth. Enamel fluorosis, with a prevalence of 12–33%, may occur
at low levels of fluoride in drinking-water, depending on total intake, and will only
be detectable by specialist examination. It can be difficult to achieve effective
fluoride-based caries prevention programmes at the community level without some
degree of very mild or mild enamel fluorosis.

 In skeletal fluorosis, fluoride accumulates progressively in the bone over a number

of years. Early symptoms include stiffness and pain in the joints. Crippling skeletal
fluorosis is associated with osteosclerosis, calcification of tendons and ligaments,
and bone deformities. There is evidence from India and China of excess risk of
skeletal fluorosis and bone fractures at a total fluoride intake of 14 mg/day, and
suggestive evidence of increased risk of skeleton effects at a total intake above
about 6 mg/day.

 While the global prevalence of dental and skeletal fluorosis is not entirely clear,
based on analysis of data published between 1953 and 2000, it was estimated in
2006 that excessive fluoride concentrations in drinking-water have caused tens of millions of cases
of dental and skeletal fluorosis worldwide over a range of years.
 Children whose teeth and bones are still developing are most susceptible; poor
nutritional status can aggravate this situation.

 Although administration of very high doses of fluoride to rats in a two-year cancer

bioassay was associated with increased incidence of osteosarcoma, there is no
evidence in recent and peer-reviewed publications that fluoride levels in drinking water aimed at
controlling dental caries is associated with increased risk of bone
cancers in humans. No relation was found between rates of Down syndrome or
congenital malformation and the consumption of fluoridated drinking-water, based
on review of several epidemiological studies of pregnancy outcome.

Dental fluorosis
Exposure to high concentrations of fluoride during childhood, when teeth are developing, can result
in mild dental fluorosis. There will be tiny white streaks or specks in the enamel of the tooth.

This does not affect the health of the teeth, but the discoloration may be noticeable.

Breastfeeding infants or making up formula milk with fluoride-free water can help protect small children
from fluorosis.

Children below the age of 6 years should not use a mouthwash that contains fluoride. Children should
be supervised when brushing their teeth to ensure they do not swallow toothpaste.

Skeletal fluorosis

Excess exposure to fluoride can lead to a bone disease Trusted Source known as skeletal fluorosis. Over
many years, this can result in pain and damage to bones and joints.

The bones may become hardened and less elastic, increasing the risk of fractures. If the bones thicken
and bone tissue accumulates, this can contribute to impaired joint mobility.

Thyroid problems
In some cases, excess fluoride can damage the parathyroid gland. This can result in
hyperparathyroidism, which involves uncontrolled secretion of parathyroid hormones.

This can result in a depletion of calcium in bone structures and higher-than-normal concentrations of
calcium in the blood.

Lower calcium concentrations in bones make them more susceptible to fractures.

Neurological problems
In 2017, a report was published suggesting that exposure to fluoride before birth could lead toTrusted
Source poorer cognitive outcomes in the future.

The researchers measured fluoride levels in 299 women during pregnancy and in their children between
the ages of 6 and 12 years. They tested cognitive ability at the ages of 4 years and between 6 and 12
years. Higher levels of fluoride were associated with lower scores on IQ tests.
In 2014, fluoride was documented as a neurotoxin that could be hazardousTrusted Source to child
development, along with 10 other industrial chemicals, including lead, arsenic, toluene, and
methylmercury.

Other health problems

According to the International Association of Oral Medicine and Toxicology (IAOMT), an organization
that campaigns against the use of added fluoride, it may also contribute to the following health
problems:

 acne and other skin problems

 cardiovascular problems, including arteriosclerosis and arterial calcification, high blood
pressure, myocardial damage, cardiac insufficiency, and heart failure
 reproductive issues, such as lower fertility and early puberty in girls
 thyroid dysfunction
 conditions affecting the joints and bones, such as osteoarthritis, bone cancer, and
temporomandibular joint disorder (TMJ)
 neurological problems, possibly leading to ADHD

Fluoride poisoning
Acute, high-level exposure to fluoride can lead to:

 abdominal pain
 excessive saliva
 nausea and vomiting
 seizures and muscle spasms

This will not result from drinking tap water. It is only likely to happen Trusted Source in cases of
accidental contamination of drinking water, due, for example to an industrial fire or explosion.

It is worth remembering that many substances are harmful in large quantities but helpful in small
amounts.