Fluoride toxicity

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Fluoride poisoning
Classification and external resources
ICD-10 T59.5
DiseasesDB 29228
eMedicine emerg/181
MeSH D005458

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).[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) than lethal doses.[4] 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.[5]

Contents

Acute [edit]

Mechanism [edit]

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

Sources [edit]

Historically, most cases of acute fluoride toxicity have followed accidental ingestion of sodium fluoride based insecticides or rodenticides.[7] Currently, in advanced countries, most cases of fluoride exposure are due to the ingestion of dental fluoride products.[8] Although exposure to these product does not often cause toxicity, in one study 30% of children exposed to fluoride dental products developed mild symptoms.[8] Other sources include glass-etching or chrome-cleaning agents like ammonium bifluoride or hydrofluoric acid,[9][10] 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]

Organofluorine compounds [edit]

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 [edit]

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.[11]

In 2011 the National Poison Data System reported 21,513 incidence of poisoning from tooth paste containing fluoride. [12]

Chronic toxicity [edit]

World map with several land areas highlighted, especially in China, India, east Africa, southwest U.S., and Argentina.
Geographical areas associated with groundwater having over 1.5 mg/L of naturally occurring fluoride, which is above recommended levels.[13]

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.[5]

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.[14]

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.[15]

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.[16] However, in 2006, a 12-person committee of the US National Research Council (NRC) reviewed the health risks associated with fluoride consumption[17] 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.[18][19] U.S. government officials lowered recommended limits for fluoride in water on Friday Jan. 7, 2011, saying some children may be getting tooth damage from too much. The Health and Human Services Department lowered its recommended levels to 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

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

  • A weakening of bones, leading to an increase in hip and wrist fracture. At the level used in fluoridated water, decreased fractures are expected,[14] 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 relationship at these levels.[17]:170
  • 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.[17]:281 Those with impaired kidney function are more susceptible to adverse effects.[17]:292
  • Four epidemiological studies have noted a correlation between increased fluoride and low IQ.[17]:205–223 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.[17]:208 Two Chinese meta-analyses which included the previously mentioned studies have also noted this correlation.[20][21] 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".[17]:219 This topic has been identified previously as cause for concern.[22] The NRC noted that rats administered fluoride had twice as much aluminum in their brains.[17]: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,[23] and a 2002 study found that fluoride increased the urinary excretion of aluminum.[24]
  • Fluoride's suppressive effect on the thyroid is more severe when iodine is deficient, and fluoride is associated with lower levels of iodine.[22] 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.[17]:263 Its mechanisms and effects on the endocrine system remain unclear.[17]:266

History [edit]

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".[25] 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.[26] The effects of fluoride-rich ground water became recognized in the 1990s.[5]

References [edit]

  1. ^ Gosselin, RE; Smith RP, Hodge HC (1984). Clinical toxicology of commercial products. Baltimore (MD): Williams & Wilkins. pp. III–185–93. ISBN 0-683-03632-7. 
  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 92-4-157227-2. 
  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 c 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. ^ Baez, Ramon 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/Pan American Journal of Public Health 7 (4): 242–248. 
  7. ^ Nochimson G. (2008). Toxicity, Fluoride. eMedicine. Retrieved 2008-12-28.
  8. ^ a b Augenstein WL, Spoerke DG, Kulig KW, et al. (November 1991). "Fluoride ingestion in children: a review of 87 cases". Pediatrics 88 (5): 907–12. PMID 1945630. 
  9. ^ Wu ML, Deng JF, Fan JS (November 2010). "Survival after hypocalcemia, hypomagnesemia, hypokalemia and cardiac arrest following mild hydrofluoric acid burn". Clinical Toxicology (Philadelphia, Pa.) 48 (9): 953–5. doi:10.3109/15563650.2010.533676. PMID 21171855. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ {{cite journal | title = The 2011 Annual Report of the American Association of Poison Control Centers | author = ALVIN C. BRONSTEIN , MD; DANIEL A. SPYKER , PHD, MD; LOUIS R. CANTILENA , JR, MD, PHD, BARRY H. RUMACK , MD; and RICHARD C. DA | journal = National Poison Data System (NPDS) | year = 2011 | volume = 29 | pages = 190 | doi = 10.3109/15563650.2012.746424 } }
  13. ^ National Health and Medical Research Council (Australia). A systematic review of the efficacy and safety of fluoridation [PDF]. 2007 [cited 2009-10-13]. ISBN 1-86496-415-4. Summary: Yeung CA. A systematic review of the efficacy and safety of fluoridation. Evid Based Dent. 2008;9(2):39–43. doi:10.1038/sj.ebd.6400578. PMID 18584000. Lay summary: NHMRC, 2007.
  14. ^ a b McDonagh MS, Whiting PF, Wilson PM et al. (2000). "Systematic review of water fluoridation" (PDF). BMJ 321 (7265): 855–9. doi:10.1136/bmj.321.7265.855. PMC 27492. PMID 11021861.  The full report is at: McDonagh MS, Whiting PF, Bradley M et al. (2000). A systematic review of water fluoridation (PDF). CRD Report 18. NHS Centre for Reviews and Dissemination. 
  15. ^ 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. 
  16. ^ Fluoride in Drinking Water, EPA Fact Sheet, December 1993
  17. ^ a b c d e f g h i j National Research Council (2006). Fluoride in Drinking Water: A Scientific Review of EPA's Standards. Washington, DC: National Academies Press. ISBN 0-309-10128-X. Lay summary – NRC (September 24, 2008). . See also CDC's statement on this report.
  18. ^ EPA: Community Water Fluoridation, FAQ
  19. ^ EPA: Setting Standards for Safe Drinking Water
  20. ^ Liu M, Qian C (December 2008). "[Effect of endemic fluorosis on children's intelligence development: a Meta analysis.]". Zhongguo Dang Dai Er Ke Za Zhi (in Chinese) 10 (6): 723–5. PMID 19102839. 
  21. ^ Tang QQ, Du J, Ma HH, Jiang SJ, Zhou XJ (2008). "Fluoride and children's intelligence: a meta-analysis". Biol Trace Elem Res 126 (1–3): 115–20. doi:10.1007/s12011-008-8204-x. PMID 18695947. 
  22. ^ a b Strunecká A, Strunecký O, Patocka J (2002). "Fluoride plus aluminum: useful tools in laboratory investigations, but messengers of false information". Physiol Res 51 (6): 557–64. PMID 12511178. 
  23. ^ Li L (2003). "The biochemistry and physiology of metallic fluoride: action, mechanism, and implications". Crit. Rev. Oral Biol. Med. 14 (2): 100–14. doi:10.1177/154411130301400204. PMID 12764073.  Free full-text.
  24. ^ Chiba J, Kusumoto M, Shirai S, Ikawa K, Sakamoto S (March 2002). "The influence of fluoride ingestion on urinary aluminum excretion in humans". Tohoku J. Exp. Med. 196 (3): 139–49. doi:10.1620/tjem.196.139. PMID 12002270.  Free full-text.
  25. ^ Dean T.H. (1938). Fluorine Intoxication. Am J Public Health Nations Health 28: 1008–1009. Free full text.
  26. ^ Division of Oral Health, National Center for Chronic Disease Prevention and Health Promotion, CDC. Achievements in public health, 1900–1999: Fluoridation of drinking water to prevent dental caries. MMWR Morb Mortal Wkly Rep. 1999;48(41):933–40. Contains H. Trendley Dean, D.D.S. Reprinted in: JAMA. 2000;283(10):1283–6. doi:10.1001/jama.283.10.1283. PMID 10714718.
Inorganic
Nonmetals / halogen compounds
Organic
CHO
Pharmaceutical
drugs
Biological
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toxin,
foodborne illness)
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