Fluoride poisoning
Encyclopedia
In high concentrations, soluble fluoride
salts are toxic and skin or eye contact with high concentrations of many fluoride salts is dangerous. Referring to a common salt of fluoride, sodium fluoride
(NaF), the lethal dose for most adult humans is estimated at 5 to 10 g (which is equivalent to 32 to 64 mg/kg elemental fluoride/kg body weight). A toxic dose that may lead to adverse health effects is estimated at 3 to 5 mg/kg of elemental fluoride. Ingestion of fluoride can produce gastrointestinal discomfort at doses at least 15 to 20 times lower (0.2–0.3 mg/kg) than lethal doses. Although helpful for dental health in low dosage, chronic exposure to fluoride in large amounts interferes with bone formation. In this way, the greatest examples of fluoride poisoning arises from fluoride-rich ground water.
through the urine. Urine tests
have been used to ascertain rates of excretion in order to set upper limits in exposure to fluoride compounds and associated detrimental health effects. Ingested fluoride initially acts locally on the intestinal mucosa, where it forms hydrofluoric acid in the stomach. Thereafter it binds calcium and interferes with various enzymes.
, industrial exposure to fluxes
used to promote the flow of a molten metal on a solid surface, volcanic ejecta
(for example, in cattle grazing after an 1845–1846 eruption of Hekla
and the 1783–1784 flood basalt eruption of Laki), and metal cleaners. Malfunction of water fluoridation equipment has happened several times, including a notable incident in Alaska.
must release fluoride (F−) ions. Whereas most organofluorine compounds may not release F− because of the strength of the carbon–fluorine bond
and its tendency to strengthen as more fluorine
atoms are added to a carbon
, others do, such as methoxyflurane
. The fluorine atom is pervasive in drugs, e.g. Prozac
, and many other substances such as freon, Teflon, and blood serum
(PFOS, PFOA, and PFNA).
, diarrhea
, dysphagia
, hypersalivation
, mucosal injury, nausea
, vomiting
. Electrolyte
abnormalities including hyperkalemia
, hypocalcemia, hypoglycemia
, and hypomagnesemia
may occur. Neurological symptoms include headache
, muscle weakness
, hyperactive reflexes, muscular spasm
s, paresthesia
seizures, tetanic contraction
s, and tremor
s. In severe cases, multi-organ failure will occur. Death typically results from cardiac arrest
, shock, widening of QRS
, and various arrhythmias occur.
The only generally accepted adverse effect of fluoride at levels used for water fluoridation
is dental fluorosis
, which can alter the appearance of children's teeth during tooth development
; this is mostly mild and usually only an aesthetic concern. Compared to unfluoridated water, fluoridation to 1 mg/L is estimated to cause fluorosis in one of every 6 people (range 4–21), and to cause fluorosis of aesthetic concern in one of every 22 people (range 13.6–∞). Here, "aesthetic concern" is a term used in a standardized scale based on what adolescents would find unacceptable, as measured by a 1996 study of British 14-year-olds.
Consumption of fluoride at levels beyond those used in fluoridated water for a long period of time causes skeletal fluorosis
. In some areas, particularly the Asian subcontinent, skeletal fluorosis is endemic. It is known to cause irritable-bowel symptoms and joint pain. Early stages are not clinically obvious, and may be misdiagnosed as (seronegative) rheumatoid arthritis
or ankylosing spondylitis
.
Other adverse effects may be possible at fluoride intake levels above the recommended dosage, and defluoridation is recommended in these cases. In 1986, the United States Environmental Protection Agency
(EPA) established a maximum contaminant level
(MCL) for fluoride at a concentration of 4 milligrams per liter (mg/L), which is the legal limit of fluoride allowed in the water. In 1993, a review by the National Academy of Sciences
conducted at the behest of EPA concluded that the 4 mg/L MCL was appropriate. However, in 2006, a 12-person committee of the US National Research Council
(NRC) reviewed the health risks associated with fluoride consumption and came to the differing conclusion that the MCL should be lowered. In response to these studies, the EPA has made no change to the MCL.
Excess fluoride consumption has been studied as a factor in the following:
Fluoride
Fluoride is the anion F−, the reduced form of fluorine when as an ion and when bonded to another element. Both organofluorine compounds and inorganic fluorine containing compounds are called fluorides. Fluoride, like other halides, is a monovalent ion . Its compounds often have properties that are...
salts are toxic and skin or eye contact with high concentrations of many fluoride salts is dangerous. Referring to a common salt of fluoride, sodium fluoride
Sodium fluoride
Sodium fluoride is an inorganic chemical compound with the formula NaF. A colorless solid, it is a source of the fluoride ion in diverse applications. Sodium fluoride is less expensive and less hygroscopic than the related salt potassium fluoride....
(NaF), the lethal dose for most adult humans is estimated at 5 to 10 g (which is equivalent to 32 to 64 mg/kg elemental fluoride/kg body weight). A toxic dose that may lead to adverse health effects is estimated at 3 to 5 mg/kg of elemental fluoride. Ingestion of fluoride can produce gastrointestinal discomfort at doses at least 15 to 20 times lower (0.2–0.3 mg/kg) than lethal doses. Although helpful for dental health in low dosage, chronic exposure to fluoride in large amounts interferes with bone formation. In this way, the greatest examples of fluoride poisoning arises from fluoride-rich ground water.
Mechanism
Like most soluble materials, fluoride compounds are readily absorbed by the stomach and intestines, and excretedExcretion
Excretion is the process by which waste products of metabolism and other non-useful materials are eliminated from an organism. This is primarily carried out by the lungs, kidneys and skin. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell...
through the urine. Urine tests
Urinalysis
A urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...
have been used to ascertain rates of excretion in order to set upper limits in exposure to fluoride compounds and associated detrimental health effects. Ingested fluoride initially acts locally on the intestinal mucosa, where it forms hydrofluoric acid in the stomach. Thereafter it binds calcium and interferes with various enzymes.
Sources
Historically, most cases of fluoride toxicity have followed accidental ingestion of sodium fluoride based insecticides or rodenticides. Currently, in advanced countries, most cases of fluoride exposure are due to the ingestion of dental fluoride products. Although exposure to these product does not often cause toxicity, in one study 30% of children exposed to fluoride dental products developed mild symptoms. Other sources include glass-etching or chrome-cleaning agents like ammonium bifluoride or hydrofluoric acidHydrofluoric acid
Hydrofluoric acid is a solution of hydrogen fluoride in water. It is a valued source of fluorine and is the precursor to numerous pharmaceuticals such as fluoxetine and diverse materials such as PTFE ....
, industrial exposure to fluxes
Flux (metallurgy)
In metallurgy, a flux , is a chemical cleaning agent, flowing agent, or purifying agent. Fluxes may have more than one function at a time...
used to promote the flow of a molten metal on a solid surface, volcanic ejecta
Ejecta
Ejecta can mean:*In volcanology, particles that came out of a volcanic vent, traveled through the air or under water, and fell back on the ground surface or on the ocean floor...
(for example, in cattle grazing after an 1845–1846 eruption of Hekla
Hekla
Hekla is a stratovolcano located in the south of Iceland with a height of . Hekla is one of Iceland's most active volcanoes; over 20 eruptions have occurred in and around the volcano since 874. During the Middle Ages, Icelanders called the volcano the "Gateway to Hell."Hekla is part of a volcanic...
and the 1783–1784 flood basalt eruption of Laki), and metal cleaners. Malfunction of water fluoridation equipment has happened several times, including a notable incident in Alaska.
Organofluorine compounds
Organofluorine compounds only rarely release F− under biological conditions and thus are rarely sources of fluoride poisoning. In order for fluoride poisoning to occur, a compoundChemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
must release fluoride (F−) ions. Whereas most organofluorine compounds may not release F− because of the strength of the carbon–fluorine bond
Carbon–fluorine bond
The carbon–fluorine bond is a bond between carbon and fluorine that is a component of all organofluorine compounds. It is the strongest single bond in organic chemistry—and relatively short—due to its partial ionic character. The bond also strengthens and shortens as more fluorines are...
and its tendency to strengthen as more fluorine
Fluorine
Fluorine is the chemical element with atomic number 9, represented by the symbol F. It is the lightest element of the halogen column of the periodic table and has a single stable isotope, fluorine-19. At standard pressure and temperature, fluorine is a pale yellow gas composed of diatomic...
atoms are added to a carbon
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
, others do, such as methoxyflurane
Methoxyflurane
Methoxyflurane is a halogenated ether that was in clinical use as an volatile inhalational anesthetic from its introduction by Joseph F. Artusio et al in 1960 until around 1974. It was first synthesized in the late 1940s by William T...
. The fluorine atom is pervasive in drugs, e.g. Prozac
Fluoxetine
Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
, and many other substances such as freon, Teflon, and blood serum
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
(PFOS, PFOA, and PFNA).
Symptoms
Poisoning comes from ingesting a large amount of fluoride in a short period of time. Ingesting 3–5 mg/kg may cause symptoms to appear, while the estimated lethal dose is 5–10 g (32–64 mg/kg) in adults and 16 mg/kg in children. Severity of symptoms depends upon the amount of fluoride ingested. These include abdominal painAbdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, dysphagia
Dysphagia
Dysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia....
, hypersalivation
Hypersalivation
Hypersalivation is excessive production of saliva. It has also been defined as increased amount of saliva in the mouth, which may also be caused by decreased clearance of saliva....
, mucosal injury, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
. Electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
abnormalities including hyperkalemia
Hyperkalemia
Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
, hypocalcemia, hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
, and hypomagnesemia
Hypomagnesemia
Hypomagnesemia is an electrolyte disturbance in which there is an abnormally low level of magnesium in the blood. Usually a serum level less than 0.7 mmol/L is used as reference. The prefix hypo- means low . The middle 'magnes' refers to magnesium...
may occur. Neurological symptoms include headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, muscle weakness
Muscle weakness
Muscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...
, hyperactive reflexes, muscular spasm
Spasm
In medicine a spasm is a sudden, involuntary contraction of a muscle, a group of muscles, or a hollow organ, or a similarly sudden contraction of an orifice. It is sometimes accompanied by a sudden burst of pain, but is usually harmless and ceases after a few minutes...
s, paresthesia
Paresthesia
Paresthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...
seizures, tetanic contraction
Tetanic contraction
A tetanic contraction occurs when a motor unit has been maximally stimulated by its motor neuron. This occurs when a muscle's motor unit is stimulated at a sufficiently high frequency of multiple impulses. Each stimulus causes a twitch. If stimuli are delivered slow enough, the tension in the...
s, and tremor
Tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...
s. In severe cases, multi-organ failure will occur. Death typically results from cardiac arrest
Cardiac arrest
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
, shock, widening of QRS
Electrical conduction system of the heart
The normal intrinsic electrical conduction of the heart allows electrical propagation to be transmitted from the Sinoatrial Node through both atria and forward to the Atrioventricular Node. Normal/baseline physiology allows further propagation from the AV node to the ventricle or Purkinje Fibers...
, and various arrhythmias occur.
Fluoride in toothpaste
Children may experience gastrointestinal distress upon ingesting sufficient amounts of flavored toothpaste. Between 1990 and 1994, over 628 people, mostly children, were treated after ingesting too much fluoride from their toothpaste. Gastrointestinal symptoms appear to be the most common problem reported.Chronic toxicity
In India an estimated 60 million people have been poisoned by well water contaminated by excessive fluoride, which is dissolved from the granite rocks. The effects are particularly evident in the bone deformations of children. Similar or larger problems are anticipated in other countries including China, Uzbekistan, and Ethiopia.The only generally accepted adverse effect of fluoride at levels used for water fluoridation
Water fluoridation
Water fluoridation is the controlled addition of fluoride to a public water supply to reduce tooth decay. Fluoridated water has fluoride at a level that is effective for preventing cavities; this can occur naturally or by adding fluoride...
is dental fluorosis
Dental fluorosis
Dental fluorosis is a developmental disturbance of dental enamel caused by excessive exposure to high concentrations of fluoride during tooth development. The risk of fluoride overexposure occurs between the ages of 3 months and 8 years. In its mild forms , fluorosis often appears as unnoticeable,...
, which can alter the appearance of children's teeth during tooth development
Tooth development
Tooth development or odontogenesis is the complex process by which teeth form from embryonic cells, grow, and erupt into the mouth. Although many diverse species have teeth, non-human tooth development is largely the same as in humans...
; this is mostly mild and usually only an aesthetic concern. Compared to unfluoridated water, fluoridation to 1 mg/L is estimated to cause fluorosis in one of every 6 people (range 4–21), and to cause fluorosis of aesthetic concern in one of every 22 people (range 13.6–∞). Here, "aesthetic concern" is a term used in a standardized scale based on what adolescents would find unacceptable, as measured by a 1996 study of British 14-year-olds.
Consumption of fluoride at levels beyond those used in fluoridated water for a long period of time causes skeletal fluorosis
Skeletal fluorosis
Skeletal fluorosis is a bone disease caused by excessive consumption of fluoride. In advanced cases, skeletal fluorosis causes pain and damage to bones and joints.-Forms:...
. In some areas, particularly the Asian subcontinent, skeletal fluorosis is endemic. It is known to cause irritable-bowel symptoms and joint pain. Early stages are not clinically obvious, and may be misdiagnosed as (seronegative) rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
or ankylosing spondylitis
Ankylosing spondylitis
Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...
.
Other adverse effects may be possible at fluoride intake levels above the recommended dosage, and defluoridation is recommended in these cases. In 1986, the United States Environmental Protection Agency
United States Environmental Protection Agency
The U.S. Environmental Protection Agency is an agency of the federal government of the United States charged with protecting human health and the environment, by writing and enforcing regulations based on laws passed by Congress...
(EPA) established a maximum contaminant level
Maximum Contaminant Level
Maximum Contaminant Levels are standards that are set by the United States Environmental Protection Agency for drinking water quality. An MCL is the legal threshold limit on the amount of a substance that is allowed in public water systems under the Safe Drinking Water Act...
(MCL) for fluoride at a concentration of 4 milligrams per liter (mg/L), which is the legal limit of fluoride allowed in the water. In 1993, a review by the National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
conducted at the behest of EPA concluded that the 4 mg/L MCL was appropriate. However, in 2006, a 12-person committee of the US National Research Council
United States National Research Council
The National Research Council of the USA is the working arm of the United States National Academies, carrying out most of the studies done in their names.The National Academies include:* National Academy of Sciences...
(NRC) reviewed the health risks associated with fluoride consumption and came to the differing conclusion that the MCL should be lowered. In response to these studies, the EPA has made no change to the MCL.
Excess fluoride consumption has been studied as a factor in the following:
- A weakening of boneBoneBones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
s, leading to an increase in hip and wrist fracture. At the level used in fluoridated water, decreased fractures are expected, but the U.S. National Research Council found the overall evidence "suggestive but inadequate for drawing firm conclusions about the risk or safety of exposures at [2 mg/L]", but states that fractures do seem to increase as fluoride is increased from 1 mg/L to 4 mg/L, suggesting a "continuous exposure-effect" dose-response relationshipDose-response relationshipThe dose-response relationship, or exposure-response relationship, describes the change in effect on an organism caused by differing levels of exposure to a stressor after a certain exposure time...
at these levels.
- Adverse effects on the kidney. Within the recommended dose, no effects are expected, but chronic ingestion in excess of 12 mg/day are expected to cause adverse effects, and an intake that high is possible when fluoride levels are around 4 mg/L. Those with impaired kidney function are more susceptible to adverse effects.
- Little research has been done on possible liverLiverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
damage, although some studies suggest negative effects at chronic ingestion of 23 mg/day.
- Chromosomal damage and interference with DNADNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
repair. Overall, the literature from in vitro and rodent studies does not indicate genotoxicity, but the in vivo human studies are inconsistent.
- Four epidemiological studies have noted a correlation between increased fluoride and low IQ. The most rigorous of these compared an area with mean water concentration of 0.36 ± 0.15 mg/L (range 0.18–0.76 mg/L) to an area with 2.47 ± 0.79 mg/L (range 0.57–4.50 mg/L). Most of these studies did not publish important details, making them difficult to evaluate. If these correlations are caused by fluoride, the mechanism is not known, but the National Research Council speculates that effects on the thyroid could lead to poor test results. Two Chinese meta-analyses which included the previously mentioned studies have also noted this correlation. The high-fluoride areas studied had fluoride levels above those used in water fluoridation.
- The NRC report stated that "many of the untoward effects of fluoride are due to the formation of AlFx [aluminum fluoride] complexes". This topic has been identified previously as cause for concern. The NRC noted that rats administered fluoride had twice as much aluminum in their brains. When water (1 ppm fluoride) is boiled in aluminum cookware more aluminum is leached and more aluminum fluoride complexes are formed. However, an epidemiological study found that a high-fluoride area had one-fifth the Alzheimer's that a low-fluoride area had, and a 2002 study found that fluoride increased the urinary excretion of aluminum.
- Fluoride's suppressive effect on the thyroid is more severe when iodine is deficient, and fluoride is associated with lower levels of iodine. Thyroid effects in humans were associated with fluoride levels 0.05–0.13 mg/kg/day when iodine intake was adequate and 0.01–0.03 mg/kg/day when iodine intake was inadequate. Its mechanisms and effects on the endocrine system remain unclear.