Fluoride poisoning
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| Fluoride poisoning | |
|---|---|
| Classification and external resources | |
| ICD-10 | T59.5 |
| DiseasesDB | 29228 |
| eMedicine | emerg/181 |
| MeSH | D005458 |
| Part of a series on |
| Toxicology and poison |
|---|
| Toxicology (Forensic) · Toxinology · History of poison |
| Concepts |
| Poison · Venom · Toxicant (Toxin) · Acceptable daily intake · Acute toxicity · Bioaccumulation · Biomagnification · Fixed Dose Procedure · LD50 · Lethal dose · Toxic capacity · Toxicity Class |
| Treatments |
| Antidote · Gastric lavage · Whole bowel irrigation · Activated carbon · Cathartic · Hemodialysis · Chelation therapy · Hemoperfusion |
| Incidents |
| Bradford · Minamata · Niigata Alexander Litvinenko · Bhopal · 2007 pet food recalls · Seveso disaster · List of poisonings |
| Related topics |
| Hazard symbol · Carcinogen Mutagen · List of Extremely Hazardous Substances · Biological warfare · Food safety |
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, NaF, the lethal dose for most adult humans is estimated at 1–10 grams.[1] A lethal dose is approximately 28 mg per kilogram of body mass.[2]
Contents |
[edit] Acute
[edit] Mechanism
Like most soluble materials, fluoride compounds are readily absorbed by the stomach, intestines and excreted through the urine. Trace amounts are incorporated in bone. 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.[3] Ingested fluoride initially acts locally on the intestinal mucosa, where it forms hydrofluoric acid in the stomach.[4] Thereafter it binds calcium and interferes with various enzymes.[4]
[edit] Possible sources
Historically, most cases of fluoride poisoning have been caused by accidental ingestion of insecticides[5] or rodenticides (e.g. sodium fluoroacetate[6]) containing fluoride. Currently most cases are due to the ingestion of toothpaste.[4] Other sources include glass-etching or chrome-cleaning agents like ammonium bifluoride, 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 a 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.[7]
[edit] Organofluorine compounds
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, 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). Organofluorine compounds, however, that are fluoroalkane based do not release F− under biological conditions because of their stability.
[edit] 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.[4] Severity of symptoms depends upon the amount of fluoride ingested. These include abdominal pain, 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 spasms, paresthesia seizures, tetanic contractions, and tremors. In severe cases, multi organ failure will occur. Death typically results from cardiac arrest, shock, widening of QRS, and various arrhythmias occur.[4]
[edit] Lethal levels
As of April 7, 1997, the United States FDA (Food & Drug Administration) required that all fluoride toothpastes sold in the U.S. carry the following poison warning:[citation needed]
WARNING: Keep out of reach of children under 6 years of age. If you accidentally swallow more than used for brushing, seek professional help or contact a poison control center immediately.
Potentially fatal dose = 5 mg of fluoride per kg of bodyweight.
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.[7][8] A 2-year-old, for example, may experience gastrointestinal distress upon ingesting sufficient amounts of flavored toothpaste. Between 1989 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.[9]
[edit] Chronic toxicity
The only generally accepted adverse effect of fluoride at levels used for water fluoridation is dental and skeletal fluorosis. which can alter the appearance of children's teeth during tooth development; this is mostly mild and not usually of 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.[10]
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.[11]
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 litre (mg/L), which is the legal limit of natural fluoride allowed in the water. In 2006, a 12-person committee of the US National Research Council (NRC) reviewed the health risks associated with fluoride consumption[12] and unanimously concluded that the maximum contaminant level of 4 mg/L should be lowered. The EPA has yet to act on the NRC's recommendation.[13][14] The limit was previously 1.4 – 2.4 mg/L, but it was raised to 4 mg/L in 1985.[15]
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,[10] 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.[12]: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.[12]:281 Those with impaired kidney function are more susceptible to adverse effects.[12]:292
- Little research has been done on possible liver damage, although some studies suggest negative effects at chronic ingestion of 23 mg/day.[12]:292
- Chromosomal damage and interference with DNA repair.[12]:304 Overall, the literature from in vitro and rodent studies does not indicate genotoxicity, but the in vivo human studies are inconsistent.[12]:316
- Four epidemiological studies have noted a correlation between increased fluoride and low IQ.[12]: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 milligrams per liter [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.[12]:208 Two Chinese meta-analyses which included the previously mentioned studies have also noted this correlation.[16][17] 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".[12]:219 This topic has been identified previously as cause for concern.[18] The NRC noted that rats administered fluoride had twice as much aluminum in their brains.[12]: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,[19] and a 2002 study found that fluoride increased the urinary excretion of aluminum.[20]
- Fluoride's suppressive effect on the thyroid is more severe when iodine is deficient, and fluoride is associated with lower levels of iodine.[18] 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.[12]:263 Its mechanisms and effects on the endocrine system remain unclear.[12]:266
[edit] History
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".[21]
[edit] References
- ^ Jean Aigueperse, Paul Mollard, Didier Devilliers, Marius Chemla, Robert Faron, Renée Romano, Jean Pierre Cuer, “Fluorine Compounds, Inorganic” in Ullmann’s Encyclopedia of Industrial Chemistry 2005 Wiley-VCH, Weinheim. DOI 10.1002/14356007.a11 307
- ^ Robert H. Dreisbach PhD, “Fluorine, Hydrogen Fluoride & Derivatives” in the Handbook of Poisoning 9th Edition 1977 Lange Medical Publications ISBN 0-87041-071-7
- ^ Baez, Ramon J.; Baez, Martha X.; Marthaler, Thomas M. 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, Volume 7, Number 4, April 2000, pp. 242-248 (7). http://www.ingentaconnect.com/content/paho/pajph/2000/00000007/00000004/art00005
- ^ a b c d e Nochimson G. (2008). Toxicity, Fluoride. eMedicine. Retrieved 2008-12-28.
- ^ Augenstein, WL (1991). "Fluoride ingestion in children: a review of 87 cases". Pediatrics 88 (5): 907–912. http://pediatrics.aappublications.org/cgi/content/abstract/88/5/907. Retrieved 2009-04-17.
- ^ Green W (July 2004). "The use of 1080 for pest control" (pdf). The Animal Health Board and The Department of Conservation. http://www.doc.govt.nz/upload/documents/conservation/threats-and-impacts/animal-pests/use-of-1080-04.pdf. Retrieved 2008-12-16.
- ^ 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. PMID 8259189. http://content.nejm.org/cgi/content/full/330/2/95.
- ^ Kenji Akiniwa (1997). "Re-examination of acute toxicity of fluoride". Fluoride 30 (2): 89–104. http://www.fluoride-journal.com/97-30-2/302-89.htm.
- ^ 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:.
- ^ a b McDonagh MS, Whiting PF, Wilson PM et al. (2000). "Systematic review of water fluoridation" (PDF). BMJ 321 (7265): 855–9. doi:. PMID 11021861. PMC 27492. http://www.bmj.com/cgi/reprint/321/7265/855.pdf. The full report is at: McDonagh MS, Whiting PF, Bradley M et al. (2000) (PDF). A systematic review of water fluoridation. CRD Report 18. NHS Centre for Reviews and Dissemination. http://www.york.ac.uk/inst/crd/pdf/fluorid.pdf.
- ^ Gupta R, Kumar AN, Bandhu S, Gupta S (2007). "Skeletal fluorosis mimicking seronegative arthritis". Scand. J. Rheumatol. 36 (2): 154–5. doi:. PMID 17476625.
- ^ a b c d e f g h i j k l m 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. http://books.nap.edu/catalog.php?record_id=11571#toc. Lay summary (September 24, 2008).. See also CDC's statement on this report.
- ^ EPA: Community Water Fluoridation, FAQ
- ^ EPA: Setting Standards for Safe Drinking Water
- ^ EPA Fluoride Standards: Focus on Fluorosis
- ^ Liu M, Qian C (December 2008). "[Effect of endemic fluorosis on children's intelligence development: a Meta analysis.]" (in Chinese). Zhongguo Dang Dai Er Ke Za Zhi 10 (6): 723–5. PMID 19102839.
- ^ 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:. PMID 18695947.
- ^ 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. http://www.biomed.cas.cz/physiolres/pdf/51/51_557.pdf.
- ^ Li L (2003). "The biochemistry and physiology of metallic fluoride: action, mechanism, and implications". Crit. Rev. Oral Biol. Med. 14 (2): 100–14. PMID 12764073. Free full-text.
- ^ 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. PMID 12002270. Free full-text.
- ^ Dean TH. (1938). Fluorine Intoxication. Am J Public Health Nations Health 28: 1008-1009. Free full text.
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