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Fluoride toxicity

March 18, 2023

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]

Fluoride toxicity
Other namesFluoride poisoning
SpecialtyEmergency medicine, toxicology

Recommended levels

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.[8]

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.[citation needed] 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 of 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

Main article: Skeletal fluorosis

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

Main article: Dental fluorosis

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.

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. ^ a b 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. ^ a b 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. (PDF) from the original on 2015-02-17. Retrieved 2013-09-01.
  7. ^ "Archive-It – News Releases". from the original on 2017-01-29. Retrieved 2017-09-09.
  8. ^ National Health and Medical Research Council (Australia) (2007). (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 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. 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. 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 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. 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) 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. ^ a b 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. ^ a b c d e 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. from the original on October 18, 2014. Retrieved March 27, 2009.. See also CDC's statement on this report 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. (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). (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.

External links

March 18, 2023
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improve the article by adding information on neglected viewpoints or discuss the issue on the talk page March 2015 Learn how and when to remove this template message 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 Fluoride toxicityOther namesFluoride poisoningSpecialtyEmergency medicine toxicology Contents 1 Recommended levels 2 Toxicity 2 1 Chronic 2 2 Acute 3 Occurrence 3 1 Organofluorine compounds 3 1 1 Fluoride in toothpaste 3 1 2 Fluoride in drinking water 4 Effects 4 1 Brain 4 2 Bones 4 3 Kidney 4 4 Teeth 4 5 Thyroid 4 6 Effects on aquatic organisms 5 Mechanism 6 References 7 External linksRecommended levels EditFor 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 EditChronic Edit Geographical areas associated with groundwater having over 1 5 mg L of naturally occurring fluoride which is above recommended levels 8 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 Edit 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 EditOrganofluorine compounds Edit Twenty percent of modern pharmaceuticals contain fluorine 13 These organofluorine compounds are not sources of fluoride poisoning citation needed The carbon fluorine bond is too strong to release fluoride 14 Fluoride in toothpaste Edit 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 Edit 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 of locations of potential problematic wells via the Groundwater Assessment Platform GAP 18 Effects EditExcess fluoride consumption has been studied as a factor in the following Brain Edit 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 Edit Main article Skeletal fluorosis 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 Edit 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 Edit Main article Dental fluorosis 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 Edit 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 Edit 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 EditLike 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 References Edit Gosselin RE Smith RP Hodge HC 1984 Clinical toxicology of commercial products Baltimore MD Williams amp Wilkins pp III 185 93 ISBN 978 0 683 03632 9 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 IPCS 2002 Environmental health criteria 227 Fluoride Geneva International Programme on Chemical Safety World Health Organization p 100 ISBN 978 92 4 157227 9 a b 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 a b 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 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 Archive It News Releases Archived from the original on 2017 01 29 Retrieved 2017 09 09 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 Nochimson G 2008 Toxicity Fluoride Archived 2013 10 15 at the Wayback Machine eMedicine Retrieved 2008 12 28 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 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 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 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 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 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 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 Rodriguez 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 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link Groundwater Assessment Platform GAP Archived 2021 04 21 at the Wayback Machine Choi AL Sun G Zhang Y Grandjean P 2012 Developmental fluoride neurotoxicity a systematic review and meta analysis Environ Health Perspect Systematic review amp Meta analysis 120 10 1362 8 doi 10 1289 ehp 1104912 PMC 3491930 PMID 22820538 a b 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 a b c d e 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 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 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 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 Mazze RI June 1976 Methoxyflurane nephropathy Environ Health Perspect 15 111 119 doi 10 1289 ehp 7615111 PMC 1475154 PMID 1001288 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 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 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 Strunecka A Strunecky 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 Yang H Xing R Liu S Yu H Li P February 1 2016 g 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 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 Joseph A Cotruvo Desalination Guidelines Development for Drinking Water Background PDF Archived PDF from the original on March 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