|Classification and external resources|
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). 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 arise from fluoride-rich ground water.
For optimal dental health, the World Health Organization recommends a level of fluoride from 0.5 to 1.0 mg/L (milligrams per litre), depending on climate. Adverse effects are possible at fluoride levels far above this recommended dosage. The U.S. Health and Human Services Department recommends 0.7 milligrams of fluoride per liter of water – the lower limit of the current recommended range of 0.7 to 1.2 milligrams. see:http://www.reuters.com/article/2011/01/08/us-usa-fluoride-idUSTRE7064CM20110108
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.
Historically, most cases of acute 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 acid, 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.
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 compound 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, some compounds 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).
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-containing toothpaste. "While the outcomes were generally not serious," gastrointestinal symptoms appear to be the most common problem reported.
In 2011, 21,513 incidents of exposure to tooth paste containing fluoride were reported to the National Poison Data System.
Excess fluoride consumption has been studied as a factor in the following:
Whilst fluoridated water is associated with decreased levels of fractures in a population,  toxic levels of fluoride have been associated with a weakening of bones and an increase in hip and wrist fractures. The U.S. National Research Council concludes that fractures with fluoride levels 1-4mg/L, suggesting a dose-response relationship, but states that there is "suggestive but inadequate for drawing firm conclusions about the risk or safety of exposures at [2 mg/L]".:170
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.
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.:281 Those with impaired kidney function are more susceptible to adverse effects.:292
The kidney injury is characterised by failure to concentrate urine, leading to polyuria, and subsequent dehydration with hypernatremia and hyperosmolarity. Inorganic fluoride inhibits adenylate cyclase activity required for antidiuretic hormone effect on the distal convoluted tubule of the kidney. Fluoride also stimulates intrarenal vasodilation, leading to increased medullary blood flow, which interferes with the counter current mechanism in the kidney required for concentration of urine.
Fluoride induced nephrotoxicity is dose dependent, typically requiring serum fluoride levels exceeding 50 micromoles per liter to cause clinically significant renal dysfunction, which is likely when the dose of methoxyflurane exceeds 2.5 MAC hours. (Note: "MAC hour" is the multiple of the minimum alveolar concentration (MAC) of the anesthetic used times the number of hours the drug is administered, a measure of the dosage of inhaled anesthetics.)
Elimination of fluoride depends on glomerular filtration rate. Thus, patients with renal insufficiency will maintain serum fluoride for longer period of time, leading to increased risk of fluoride induced nephrotoxicity.
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.
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.:263 Its mechanisms and effects on the endocrine system remain unclear.:266
A meta-analysis published in 2012 concluded that "children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas". It is disputed, however, whether the difference is clinically relevant and whether there were other variables that could be influencing the statistical difference. However, the authors of the original study claim the dispute is based on a misunderstanding. 
Like most soluble materials, fluoride compounds are readily absorbed by the stomach and intestines, and excreted 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.
The NRC report stated that "many of the untoward effects of fluoride are due to the formation of AlFx [aluminum fluoride] complexes".:219 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.:212 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.
Danish researcher Kaj Roholm published Fluorine Intoxication in 1937, which was praised in a 1938 review by dental researcher H. Trendley Dean as "probably the outstanding contribution to the literature of fluorine". Since that time, the fluoridation of public water has been widely implemented and has been hailed as one of the top medical achievements of the 20th Century. The effects of fluoride-rich ground water became recognized in the 1990s.
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