Fluoride toxicity

Last updated
Fluoride toxicity
Other namesFluoride poisoning
Specialty Emergency medicine, toxicology

Fluoride toxicity is a condition in which there are elevated levels of the fluoride ion in the body. Although fluoride is safe for dental health at low concentrations, sustained consumption of large amounts of soluble 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 elemental fluoride/kg body weight). [1] [2] [3] Ingestion of fluoride can produce gastrointestinal discomfort at doses at least 15 to 20 times lower (0.2–0.3 mg/kg or 10 to 15 mg for a 50 kg person) than lethal doses. [4] Although it is helpful topically for dental health in low dosage, chronic ingestion of fluoride in large amounts interferes with bone formation. In this way, the most widespread examples of fluoride poisoning arise from consumption of ground water that is abnormally fluoride-rich. [5]

Contents

For optimal dental health, the World Health Organization recommends a level of fluoride from 0.5 to 1.0 mg/L (milligrams per liter), depending on climate. [6] Fluorosis becomes possible above this recommended dosage. As of 2015, the United States Health and Human Services Department recommends a maximum of 0.7 milligrams of fluoride per liter of water – updating and replacing the previous recommended range of 0.7 to 1.2 milligrams issued in 1962. The new recommended level is intended to reduce the occurrence of dental fluorosis while maintaining water fluoridation. [7]

Toxicity

Chronic

Geographical areas associated with groundwater having over 1.5 mg/L of naturally occurring fluoride, which is above recommended levels. Groundwater-fluoride-world.svg
Geographical areas associated with groundwater having over 1.5 mg/L of naturally occurring fluoride, which is above recommended levels.

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 deformities of children. Similar or larger problems are anticipated in other countries including China, Uzbekistan, and Ethiopia. [5]

Acute

Historically, most cases of acute fluoride toxicity have followed accidental ingestion of sodium fluoride based insecticides or rodenticides. [9] Currently, in advanced countries, most cases of fluoride exposure are due to the ingestion of dental fluoride products. [10] Other sources include glass-etching or chrome-cleaning agents like ammonium bifluoride or hydrofluoric acid, [11] [12] 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. [4]

Occurrence

Organofluorine compounds

Twenty percent of modern pharmaceuticals contain fluorine. [13] These organofluorine compounds are not sources of fluoride poisoning, as the carbon–fluorine bond is too strong to release fluoride. [14]

Fluoride in toothpaste

Children may experience gastrointestinal distress upon ingesting excessive 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. [15] However given the low concentration of fluoride present in dental products, this is potentially due to consumption of other major components.

Fluoride in drinking water

Around one-third of the world's population drinks water from groundwater resources. Of this, about 10 percent, approximately 300 million people, obtains water from groundwater resources that are heavily contaminated with arsenic or fluoride. [16] These trace elements derive mainly from leaching of minerals. [17] Maps are available for locations of potential problematic wells via the Groundwater Assessment Platform (GAP). [18]

Effects

Excess fluoride consumption has been studied as a factor in the following:

Brain

Some research has suggested that high levels of fluoride exposure may adversely affect neurodevelopment in children, but the evidence is of insufficient quality to allow any firm conclusions to be drawn. [19]

Bones

Whilst fluoridated water is associated with decreased levels of fractures in a population, [20] 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 1–4 mg/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]". [21] : 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. [22]

Kidney

Fluoride induced nephrotoxicity is kidney injury due to toxic levels of serum fluoride, commonly due to release of fluoride from fluorine-containing drugs, such as methoxyflurane. [23] [24] [25]

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. [21] : 281  Those with impaired kidney function are more susceptible to adverse effects. [21] : 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 (about 1 ppm) to cause clinically significant renal dysfunction, [26] which is likely when the dose of methoxyflurane exceeds 2.5 MAC hours. [27] [28] (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 chronic kidney disease will maintain serum fluoride for longer period of time, leading to increased risk of fluoride induced nephrotoxicity.

Teeth

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–∞). [20]

Thyroid

Fluoride's suppressive effect on the thyroid is more severe when iodine is deficient, and fluoride is associated with lower levels of iodine.[ clarification needed ] [29] 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. [21] : 263  Its mechanisms and effects on the endocrine system remain unclear. [21] : 266 

Testing on mice shows that the medication gamma-Aminobutyric acid (GABA) can be used to treat fluoride toxicity of the thyroid and return normal function. [30]

Effects on aquatic organisms

Fluoride accumulates in the bone tissues of fish and in the exoskeleton of aquatic invertebrates. The mechanism of fluoride toxicity in aquatic organisms is believed to involve the action of fluoride ions as enzymatic poisons. In soft waters with low ionic content, invertebrates and fishes may develop adverse effects from fluoride concentration as low as 0.5 mg/L. Negative effects are less in hard waters and seawaters, as the bioavailability of fluoride ions is reduced with increasing water hardness [31] Seawater contains fluoride at a concentration of 1.3 mg/L. [32]

Mechanism

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. [33] Ingested fluoride initially acts locally on the intestinal mucosa, where it forms hydrofluoric acid in the stomach.

Related Research Articles

<span class="mw-page-title-main">Halogen</span> Group of chemical elements

The halogens are a group in the periodic table consisting of six chemically related elements: fluorine (F), chlorine (Cl), bromine (Br), iodine (I), and the radioactive elements astatine (At) and tennessine (Ts), though some authors would exclude tennessine as its chemistry is unknown and is theoretically expected to be more like that of gallium. In the modern IUPAC nomenclature, this group is known as group 17.

Fluoride is an inorganic, monatomic anion of fluorine, with the chemical formula F−
, whose salts are typically white or colorless. Fluoride salts typically have distinctive bitter tastes, and are odorless. Its salts and minerals are important chemical reagents and industrial chemicals, mainly used in the production of hydrogen fluoride for fluorocarbons. Fluoride is classified as a weak base since it only partially associates in solution, but concentrated fluoride is corrosive and can attack the skin.

<span class="mw-page-title-main">Skeletal fluorosis</span> Medical condition

Skeletal fluorosis is a bone disease caused by excessive accumulation of fluoride leading to weakened bones. In advanced cases, skeletal fluorosis causes painful damage to bones and joints.

<span class="mw-page-title-main">Water fluoridation</span> Addition of fluoride to a water supply to reduce tooth decay

Water fluoridation is the controlled adjustment of fluoride to a public water supply solely to reduce tooth decay. Fluoridated water contains fluoride at a level that is effective for preventing cavities; this can occur naturally or by adding fluoride. Fluoridated water operates on tooth surfaces: in the mouth, it creates low levels of fluoride in saliva, which reduces the rate at which tooth enamel demineralizes and increases the rate at which it remineralizes in the early stages of cavities. Typically a fluoridated compound is added to drinking water, a process that in the U.S. costs an average of about $1.26 per person-year. Defluoridation is needed when the naturally occurring fluoride level exceeds recommended limits. In 2011, the World Health Organization suggested a level of fluoride from 0.5 to 1.5 mg/L, depending on climate, local environment, and other sources of fluoride. Bottled water typically has unknown fluoride levels.

<span class="mw-page-title-main">Sodium fluoride</span> Ionic compound (NaF)

Sodium fluoride (NaF) is an inorganic compound with the formula NaF. It is a colorless or white solid that is readily soluble in water. It is used in trace amounts in the fluoridation of drinking water to prevent tooth decay, and in toothpastes and topical pharmaceuticals for the same purpose. In 2021, it was the 291st most commonly prescribed medication in the United States, with more than 600,000 prescriptions. It is also used in metallurgy and in medical imaging.

<span class="mw-page-title-main">Enflurane</span> Chemical compound

Enflurane is a halogenated ether. Developed by Ross Terrell in 1963, it was first used clinically in 1966. It was increasingly used for inhalational anesthesia during the 1970s and 1980s but is no longer in common use.

<span class="mw-page-title-main">Fluorine deficiency</span> Medical condition

Fluoride or fluorine deficiency is a disorder which may cause increased dental caries and possibly osteoporosis, due to a lack of fluoride in diet. Common dietary sources of fluoride include tea, grape juice, wine, raisins, some seafood, coffee, and tap water that has been fluoridated. The extent to which the condition truly exists, and its relationship to fluoride poisoning has given rise to some controversy. Fluorine is not considered to be an essential nutrient, but the importance of fluorides for preventing tooth decay is well-recognized, despite the effect is predominantly topical. Prior to 1981, the effect of fluorides was thought to be largely systemic and preeruptive, requiring ingestion. Fluoride is considered essential in the development and maintenance of teeth by the American Dental Hygienists' Association. Fluoride incorporates into the teeth to form and harden teeth enamels. This makes the teeth more acid resistant, as well as more resistant to cavity forming bacteria. Caries-inhibiting effects of fluoride were first noticed 1902, when fluoride in high concentrations was found to stain teeth and prevent tooth decay.

The water fluoridation controversy arises from political, ethical, economic, and health considerations regarding the fluoridation of public water supplies.

<span class="mw-page-title-main">Fluoride therapy</span> Medical use of fluoride

Fluoride therapy is the use of fluoride for medical purposes. Fluoride supplements are recommended to prevent tooth decay in children older than six months in areas where the drinking water is low in fluoride. It is typically used as a liquid, pill, or paste by mouth. Fluoride has also been used to treat a number of bone diseases.

<span class="mw-page-title-main">Dental fluorosis</span> Medical condition

Dental fluorosis is a common disorder, characterized by hypomineralization of tooth enamel caused by ingestion of excessive fluoride during enamel formation.

<span class="mw-page-title-main">Tobramycin</span> Chemical compound

Tobramycin is an aminoglycoside antibiotic derived from Streptomyces tenebrarius that is used to treat various types of bacterial infections, particularly Gram-negative infections. It is especially effective against species of Pseudomonas.

<span class="mw-page-title-main">H. Trendley Dean</span> American dentist (1893–1962)

Henry Trendley Dean was the first director of the United States National Institute of Dental Research and a pioneer investigator of water fluoridation in the prevention of tooth decay.

<span class="mw-page-title-main">Methoxyflurane</span> Chemical compound

Methoxyflurane, sold under the brand name Penthrox among others, is an inhaled medication primarily used to reduce pain following trauma. It may also be used for short episodes of pain as a result of medical procedures. Onset of pain relief is rapid and of a short duration. Use is only recommended with direct medical supervision.

Olaflur is a fluoride-containing substance that is an ingredient of toothpastes and solutions for the prevention of dental caries. It has been in use since 1966. Especially in combination with dectaflur, it is also used in the form of gels for the treatment of early stages of caries, sensitive teeth, and by dentists for the refluoridation of damaged tooth enamel.

<span class="mw-page-title-main">Water fluoridation by country</span>

Water fluoridation is the controlled addition of fluoride to a public water supply to reduce tooth decay, and is handled differently by country. Fluoridated water has fluoride at a level that is proven effective for preventing cavities; this can occur naturally or by adding fluoride. Fluoridated water operates on tooth surfaces: in the mouth it creates low levels of fluoride in saliva, which reduces the rate at which tooth enamel demineralizes and increases the rate at which it remineralizes in the early stages of cavities. Typically a fluoridated compound is added to drinking water, a process that in the U.S. costs an average of about $1.26 per person-year. Defluoridation is needed when the naturally occurring fluoride level exceeds recommended limits. In 2011 the World Health Organization suggested a level of fluoride from 0.5 to 1.5 mg/L, depending on climate, local environment, and other sources of fluoride. Bottled water typically has unknown fluoride levels.

<span class="mw-page-title-main">Remineralisation of teeth</span>

Tooth remineralization is the natural repair process for non-cavitated tooth lesions, in which calcium, phosphate and sometimes fluoride ions are deposited into crystal voids in demineralised enamel. Remineralization can contribute towards restoring strength and function within tooth structure.

<span class="mw-page-title-main">Water fluoridation in the United States</span>

As with some other countries, water fluoridation in the United States is a contentious issue. As of May 2000, 42 of the 50 largest U.S. cities had water fluoridation. On January 25, 1945, Grand Rapids, Michigan, became the first community in the United States to fluoridate its drinking water to prevent tooth decay.

<span class="mw-page-title-main">Biological aspects of fluorine</span>

Fluorine may interact with biological systems in the form of fluorine-containing compounds. Though elemental fluorine (F2) is very rare in everyday life, fluorine-containing compounds such as fluorite occur naturally as minerals. Naturally occurring organofluorine compounds are extremely rare. Man-made fluoride compounds are common and are used in medicines, pesticides, and materials. Twenty percent of all commercialized pharmaceuticals contain fluorine, including Lipitor and Prozac. In many contexts, fluorine-containing compounds are harmless or even beneficial to living organisms; in others, they are toxic.

Defluoridation is the downward adjustment of the level of fluoride in drinking water. Worldwide, fluoride is one of the most abundant anions present in groundwater. Fluoride is more present in groundwater than surface water mainly due to the leaching of minerals. Groundwater accounts for 98 percent of the earth's potable water. An excess of fluoride in drinking water causes dental fluorosis and skeletal fluorosis. The World Health Organization has recommended a guideline value of 1.5 mg/L as the concentration above which dental fluorosis is likely. Fluorosis is endemic in more than 20 developed and developing nations.

Topical fluorides are fluoride-containing drugs indicated in prevention and treatment of dental caries, particularly in children's primary dentitions. The dental-protecting property of topical fluoride can be attributed to multiple mechanisms of action, including the promotion of remineralization of decalcified enamel, the inhibition of the cariogenic microbial metabolism in dental plaque and the increase of tooth resistance to acid dissolution. Topical fluoride is available in a variety of dose forms, for example, toothpaste, mouth rinses, varnish and silver diamine solution. These dosage forms possess different absorption mechanisms and consist of different active ingredients. Common active ingredients include sodium fluoride, stannous fluoride, silver diamine fluoride. These ingredients account for different pharmacokinetic profiles, thereby having varied dosing regimes and therapeutic effects. A minority of individuals may experience certain adverse effects, including dermatological irritation, hypersensitivity reactions, neurotoxicity and dental fluorosis. In severe cases, fluoride overdose may lead to acute toxicity. While topical fluoride is effective in preventing dental caries, it should be used with caution in specific situations to avoid undesired side effects.

References

  1. ↑ Gosselin, RE; Smith RP; Hodge HC (1984). Clinical toxicology of commercial products. Baltimore (MD): Williams & Wilkins. pp. III–185–93. ISBN   978-0-683-03632-9.
  2. ↑ Baselt, RC (2008). Disposition of toxic drugs and chemicals in man. Foster City (CA): Biomedical Publications. pp. 636–40. ISBN   978-0-9626523-7-0.
  3. ↑ IPCS (2002). Environmental health criteria 227 (Fluoride). Geneva: International Programme on Chemical Safety, World Health Organization. p. 100. ISBN   978-92-4-157227-9.
  4. 1 2 Bradford D. Gessner; Michael Beller; John P. Middaugh; Gary M. Whitford (13 January 1994). "Acute fluoride poisoning from a public water system". New England Journal of Medicine . 330 (2): 95–99. doi: 10.1056/NEJM199401133300203 . PMID   8259189.
  5. 1 2 Pearce, Fred (2006). When the Rivers Run Dry: Journeys Into the Heart of the World's Water Crisis. Toronto: Key Porter. ISBN   978-1-55263-741-8.
  6. ↑ WHO Expert Committee on Oral Health Status and Fluoride Use (1994). Fluorides and oral health (PDF). WHO technical report series 846. Geneva: World Health Organization. ISBN   92-4-120846-5. Archived (PDF) from the original on 2015-02-17. Retrieved 2013-09-01.
  7. ↑ "Archive-It – News Releases". Archived from the original on 2017-01-29. Retrieved 2017-09-09.
  8. ↑ National Health and Medical Research Council (Australia) (2007). A systematic review of the efficacy and safety of fluoridation (PDF). ISBN   978-1-86496-415-8. Archived from the original (PDF) on 2009-10-14. Retrieved 2009-10-13. Summary: Yeung CA (2008). "A systematic review of the efficacy and safety of fluoridation". Evid-Based Dent. 9 (2): 39–43. doi: 10.1038/sj.ebd.6400578 . PMID   18584000.
  9. ↑ Nochimson G. (2008). Toxicity, Fluoride Archived 2013-10-15 at the Wayback Machine . eMedicine. Retrieved 2008-12-28.
  10. ↑ Augenstein WL, Spoerke DG, Kulig KW, et al. (November 1991). "Fluoride ingestion in children: a review of 87 cases". Pediatrics. 88 (5): 907–12. doi:10.1542/peds.88.5.907. PMID   1945630. S2CID   22106466. Archived from the original on 2010-10-02. Retrieved 2009-04-17.
  11. ↑ Wu ML, Deng JF, Fan JS (November 2010). "Survival after hypocalcemia, hypomagnesemia, hypokalemia and cardiac arrest following mild hydrofluoric acid burn". Clinical Toxicology. 48 (9): 953–5. doi:10.3109/15563650.2010.533676. PMID   21171855. S2CID   11635168.
  12. ↑ Klasaer AE, Scalzo AJ, Blume C, Johnson P, Thompson MW (December 1996). "Marked hypocalcemia and ventricular fibrillation in two pediatric patients exposed to a fluoride-containing wheel cleaner". Annals of Emergency Medicine. 28 (6): 713–8. doi:10.1016/S0196-0644(96)70097-5. PMID   8953969.
  13. ↑ Emsley J (2011). Nature's Building Blocks: An A-Z Guide to the Elements. Oxford University Press. p. 178. ISBN   978-0-19-960563-7.
  14. ↑ O'Hagan, David (March 2008). "Understanding organofluorine chemistry. An introduction to the C–F bond". Chemical Society Reviews. 37 (2): 308–319. doi:10.1039/b711844a. PMID   18197347. Archived from the original on 28 January 2021. Retrieved 21 March 2021.
  15. ↑ Jay D. Shulman; Linda M. Wells (1997). "Acute Fluoride Toxicity from Ingesting Home-use Dental Products in Children, Birth to 6 Years of Age". Journal of Public Health Dentistry. 57 (3): 150–158. doi:10.1111/j.1752-7325.1997.tb02966.x. PMID   9383753.
  16. ↑ Eawag (2015). Geogenic Contamination Handbook – Addressing Arsenic and Fluoride in Drinking Water Archived 2019-03-25 at the Wayback Machine . C. A. Johnson, A. Bretzler (eds.), Swiss Federal Institute of Aquatic Science and Technology (Eawag), Duebendorf, Switzerland.
  17. ↑ Rodríguez-Lado L, Sun G, Berg M, Zhang Q, Xue H, Zheng Q, Johnson CA (2013). "Groundwater arsenic contamination throughout China". Science. 341 (6148): 866–868. Bibcode:2013Sci...341..866R. doi:10.1126/science.1237484. PMID   23970694. S2CID   206548777. Archived from the original on 2020-10-01. Retrieved 2020-09-13.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  18. ↑ Groundwater Assessment Platform (GAP) Archived 2021-04-21 at the Wayback Machine .
  19. ↑ Choi AL, Sun G, Zhang Y, Grandjean P (2012). "Developmental fluoride neurotoxicity: a systematic review and meta-analysis". Environ. Health Perspect. (Systematic review & Meta-analysis). 120 (10): 1362–8. doi:10.1289/ehp.1104912. PMC   3491930 . PMID   22820538.
  20. 1 2 McDonagh, Marian S.; Whiting, Penny F.; Wilson, Paul M.; et al. (7 October 2000). "Systematic review of water fluoridation". BMJ. 321 (7265): 855–859. doi:10.1136/bmj.321.7265.855. PMC   27492 . PMID   11021861.
  21. 1 2 3 4 5 National Research Council (2006). Fluoride in Drinking Water: A Scientific Review of EPA's Standards. Washington, DC: National Academies Press. doi:10.17226/11571. ISBN   978-0-309-10128-8. Archived from the original on October 18, 2014. Retrieved March 27, 2009.. See also CDC's statement on this report Archived 2017-02-12 at the Wayback Machine .
  22. ↑ Gupta R, Kumar AN, Bandhu S, Gupta S (2007). "Skeletal fluorosis mimicking seronegative arthritis". Scand. J. Rheumatol. 36 (2): 154–5. doi:10.1080/03009740600759845. PMID   17476625. S2CID   39441582.
  23. ↑ Cousins MJ, Skowronski G, Plummer JL (November 1983). "Anaesthesia and the kidney". Anaesth Intensive Care. 11 (4): 292–320. doi: 10.1177/0310057X8301100402 . PMID   6359948.
  24. ↑ Baden JM, Rice SA, Mazze RI (March 1982). "Deuterated methoxyflurane anesthesia and renal function in Fischer 344 rats". Anesthesiology. 56 (3): 203–206. doi: 10.1097/00000542-198203000-00009 . PMID   7059030.
  25. ↑ Mazze RI (June 1976). "Methoxyflurane nephropathy". Environ Health Perspect. 15: 111–119. doi:10.1289/ehp.7615111. PMC   1475154 . PMID   1001288.
  26. ↑ Cousins MJ, Greenstein LR, Hitt BA, Mazze RI (1976). "Metabolism and renal effect of enflurane in man". Anesthesiology. 44 (1): 44–53. doi: 10.1097/00000542-197601000-00009 . PMID   1244774. S2CID   22903804.
  27. ↑ Van Dyke R (1973). "Biotransformation of volatile anesthetics with special emphasis on the role of metabolism in the toxicity of anesthetics". Can Anaesth Soc J. 20 (1): 21–33. doi: 10.1007/BF03025562 . PMID   4571972.
  28. ↑ White AE, Stevens WC, Eger EI II, Mazze RI, Hitt BA (1979). "Enflurane and methoxyflurane metabolism at anesthetic and at subanesthetic concentrations". Anesth Analg. 58 (3): 221–224. doi:10.1213/00000539-197905000-00011. PMID   572159. S2CID   36094568.
  29. ↑ Strunecká A, Strunecký O, Patocka J (2002). "Fluoride plus aluminum: useful tools in laboratory investigations, but messengers of false information" (PDF). Physiol Res. 51 (6): 557–64. PMID   12511178. Archived (PDF) from the original on 2017-08-08. Retrieved 2008-12-31.
  30. ↑ Yang H, Xing R, Liu S, Yu H, Li P (February 1, 2016). "γ-Aminobutyric acid ameliorates fluoride-induced hypothyroidism in male Kunming mice". Life Sci. 146: 1–7. doi:10.1016/j.lfs.2015.12.041. PMID   26724496.
  31. ↑ Camargo, Julio A. (January 2003). "Fluoride toxicity to aquatic organisms: a review". Chemosphere. 50 (3): 251–264. Bibcode:2003Chmsp..50..251C. doi:10.1016/S0045-6535(02)00498-8. PMID   12656244.
  32. ↑ Joseph A. Cotruvo. "Desalination Guidelines Development for Drinking Water: Background" (PDF). Archived (PDF) from the original on March 4, 2016. Retrieved January 26, 2015.
  33. ↑ Baez, J.; Baez, Martha X.; Marthaler, Thomas M. (2000). "Urinary fluoride excretion by children 4–6 years old in a south Texas community". Revista Panamericana de Salud Pública. 7 (4): 242–248. doi: 10.1590/s1020-49892000000400005 . PMID   10846927.
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