Lugol's iodine

Lugol's iodine, also known as aqueous iodine and strong iodine solution, is a solution of potassium iodide with iodine in water.[2] It is a medication and disinfectant used for a number of purposes.[3][4] Taken by mouth it is used to treat thyrotoxicosis until surgery can be carried out, protect the thyroid gland from radioactive iodine, and to treat iodine deficiency.[4][5] When applied to the cervix it is used to help in screening for cervical cancer.[6] As a disinfectant it may be applied to small wounds such as a needle stick injury.[3] A small amount may also be used for emergency disinfection of drinking water.[7]

Lugol's iodine
2% Lugol's iodine solution
Clinical data
Other namesPotassium triiodide, Lugol's solution, aqueous iodine, strong iodine solution[1]
AHFS/Drugs.comMonograph
License data
Routes of
administration		topical, by mouth
Identifiers
CAS Number
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.032.321
Chemical and physical data
FormulaI3K
Molar mass419.812

Side effects may include allergic reactions, headache, vomiting, and conjunctivitis.[4][1] Long term use may result in trouble sleeping and depression.[4] It should not typically be used during pregnancy or breastfeeding.[4] Lugol's iodine is a liquid made up of two parts potassium iodide for every one part elemental iodine in water.[8]

Lugol's iodine was first made in 1829 by the French physician Jean Lugol.[7][8] It is on the World Health Organization's List of Essential Medicines.[9][10] Lugol's iodine is available as a generic medication and over the counter.[1] Lugol's solution is available in different strengths of iodine. Large volumes of concentrations more than 2.2% may be subject to regulation.[11]

Uses

Medical uses

Preoperative administration of Lugol's solution decreases intraoperative blood loss during thyroidectomy in patients with Graves' disease.[12] However, it appears ineffective in patients who are already euthyroid on anti-thyroid drugs and levothyroxine.[13]

  • During colposcopy, Lugol's iodine is applied to the vagina and cervix. Normal vaginal tissue stains brown due to its high glycogen content, while tissue suspicious for cancer does not stain, and thus appears pale compared to the surrounding tissue. Biopsy of suspicious tissue can then be performed. This is called a Schiller's test.
  • Lugol's iodine may also be used to better visualize the mucogingival junction in the mouth. Similar to the method of staining mentioned above regarding a colposcopy, alveolar mucosa has a high glycogen content that gives a positive iodine reaction vs. the keratinized gingiva.[14]
  • Lugol's iodine may also be used as an oxidizing germicide, however it is somewhat undesirable in that it may lead to scarring and discolors the skin temporarily. One way to avoid this problem is by using a solution of 70% ethanol to wash off the iodine later.
  • Lugol's iodine was distributed in Polish People's Republic after the Chernobyl catastrophe, due to government not being informed of how severe the event was and overestimating radiation, and unavailability of iodine tablets.[15]

Science
  • As a mordant when performing a Gram stain. It is applied for 1 minute after staining with crystal violet, but before ethanol to ensure that gram positive organisms' peptidoglycan remains stained, easily identifying it as a gram positive in microscopy.
  • This solution is used as an indicator test for the presence of starches in organic compounds,[16] with which it reacts by turning a dark-blue/black. Elemental iodine solutions like Lugol's will stain starches due to iodine's interaction with the coil structure of the polysaccharide. Starches include the plant starches amylose and amylopectin and glycogen in animal cells. Lugol's solution will not detect simple sugars such as glucose or fructose. In the pathologic condition amyloidosis, amyloid deposits (i.e., deposits that stain like starch, but are not) can be so abundant that affected organs will also stain grossly positive for the Lugol reaction for starch.
  • It can be used as a cell stain, making the cell nuclei more visible and for preserving phytoplankton samples.
  • Lugol's solution can also be used in various experiments to observe how a cell membrane uses osmosis and diffusion.
  • Lugol's solution is also used in the marine aquarium industry. Lugol's solution provides a strong source of free iodine and iodide to reef inhabitants and macroalgae. Although the solution is thought to be effective when used with stony corals, systems containing xenia and soft corals are assumed to be particularly benefited by the use of Lugol's solution. Used as a dip for stony and soft or leather corals, Lugol's may help rid the animals of unwanted parasites and harmful bacteria. The solution is thought to foster improved coloration and possibly prevent bleaching of corals due to changes in light intensity, and to enhance coral polyp expansion. The blue colors of Acropora spp. are thought to be intensified by the use of potassium iodide. Specially packaged supplements of the product intended for aquarium use can be purchased at specialty stores and online.

Outdated uses
  • Till early 1970s, it was often recommended for use in victims of rape in order to avoid pregnancy. The idea stemmed from the fact that, in the laboratory, Lugol's iodine appeared to kill sperms even in such great dilutions as 1:32. Thus it was thought that an intrauterine application of Lugol's iodine, immediately after the event, would help avoid pregnancy.[17]

Side effects

Because it contains free iodine, Lugol's solution at 2% or 5% concentration without dilution is irritating and destructive to mucosa, such as the lining of the esophagus and stomach. Doses of 10 mL of undiluted 5% solution have been reported to cause gastric lesions when used in endoscopy.[18] The LD50 for 5% Iodine is 14,000 mg/kg (14 g/kg) in rats, and 22,000 mg/kg (22 g/kg) in mice.[19]

The World Health Organization classifies substances taken orally with an LD50 of 5–50 mg/kg as the second highest toxicity class, Class Ib (Highly Hazardous).[20] The Global Harmonized System of Classification and Labeling of Chemicals categorizes this as Category 2 with a hazard statement "Fatal if swallowed".[21] Potassium iodide is not considered hazardous.[22]

Mechanism of action

The above uses and effects are consequences of the fact that the solution is a source of effectively free elemental iodine, which is readily generated from the equilibrium between elemental iodine molecules and polyiodide ions in the solution.

History

It was historically used as a first-line treatment for hyperthyroidism, as the administration of pharmacologic amounts of iodine leads to temporary inhibition of iodine organification in the thyroid gland, caused by phenomena including the Wolff–Chaikoff effect and the Plummer effect. However it is not used to treat certain autoimmune causes of thyroid disease as iodine-induced blockade of iodine organification may result in hypothyroidism. They are not considered as a first line therapy because of possible induction of resistant hyperthyroidism but may be considered as an adjuvant therapy when used together with other hyperthyroidism medications.

Lugol's iodine has been used traditionally to replenish iodine deficiency. Because of its wide availability as a drinking-water decontaminant, and high content of potassium iodide, emergency use of it was at first recommended to the Polish government in 1986, after the Chernobyl disaster to replace and block any intake of radioactive 131
I, even though it was known to be a non-optimal agent, due to its somewhat toxic free-iodine content.[23] Other sources state that pure potassium iodide solution in water (SSKI) was eventually used for most of the thyroid protection after this accident.[24] There is "strong scientific evidence" for potassium iodide thyroid protection to help prevent thyroid cancer. Potassium iodide does not provide immediate protection but can be a component of a general strategy in a radiation emergency.[25]

Historically, Lugol's iodine solution has been widely available and used for a number of health problems with some precautions.[26] Lugol's is sometimes prescribed in a variety of alternative medical treatments.[27][28] Only since the end of the Cold War has the compound become subject to national regulation in the English-speaking world.

Society and culture

Regulation

Until 2007, in the United States, Lugol's solution was unregulated and available over the counter as a general reagent, an antiseptic, a preservative,[29] or as a medicament for human or veterinary application.

Since August 1, 2007, the DEA regulates all iodine solutions containing greater than 2.2% elemental iodine as a List I precursor because they may potentially be used in the illicit production of methamphetamine.[30] Transactions of up to one fluid ounce (30 ml) of Lugol's solution are exempt from this regulation.

Formula and manufacture
Nominal concentration Iodine (I2)
[mg/100μL[31]]		 Potassium iodide (KI)
[mg/100μL[31]]		 Total iodine
[mg/100μL[31]]
1% 1.0 2.0 2.5
2% 2.0 4.0 5.1
5% 5.0 10.0 12.6
10% 10.0 20.0 25.3

Lugol's solution is commonly available in different potencies of (nominal) 1%, 2%, 5% or 10%. Iodine concentrations greater than 2.2% are subject to US regulations.[32][33][34] If the US regulations are taken literally, their 2.2% maximum iodine concentration limits a Lugol's solution to maximum (nominal) 0.87%.

The most commonly used (nominal) 5% solution consists of 5% (wt/v) iodine (I
2) and 10% (wt/v) potassium iodide (KI) mixed in distilled water and has a total iodine content of 126.4 mg/mL. The (nominal) 5% solution thus has a total iodine content of 6.32 mg per drop of 0.05 mL; the (nominal) 2% solution has 2.53 mg total iodine content per drop.

Potassium iodide renders the elementary iodine soluble in water through the formation of the triiodide (I−
3) ion. It is not to be confused with tincture of iodine solutions, which consist of elemental iodine, and iodide salts dissolved in water and alcohol. Lugol's solution contains no alcohol.

Other names for Lugol's solution are I
2KI (iodine-potassium iodide); Markodine, Strong solution (Systemic); and Aqueous Iodine Solution BP.

In the United Kingdom in 2015, the NHS paid £9.57 per 500 ml of solution.[4]

See also

Iodine antiseptics

Reagents
  • Benedict's reagent
  • Melzer's reagent
  • Verhoeff's stain

References
  1. "Strong Iodine Solution". The American Society of Health-System Pharmacists. Archived from the original on 13 January 2017. Retrieved 8 January 2017.
  2. Kaiho, Tatsuo (2014). Iodine Chemistry and Applications. John Wiley & Sons. p. 55. ISBN 9781118466292. Archived from the original on 18 September 2017.
  3. Block, Seymour Stanton (2001). Disinfection, Sterilization, and Preservation. Lippincott Williams & Wilkins. p. 177. ISBN 9780683307405. Archived from the original on 13 January 2017.
  4. British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 493. ISBN 9780857111562.
  5. Lugol's solution Drug Information, Professional. 1994. Archived from the original on 13 January 2017. Retrieved 11 January 2017.
  6. Fokom-Domgue, Joël; Combescure, Christophe; Fokom-Defo, Victoire; et al. (3 July 2015). "Performance of alternative strategies for primary cervical cancer screening in sub-Saharan Africa: systematic review and meta-analysis of diagnostic test accuracy studies". BMJ. 351: h3084. doi:10.1136/bmj.h3084. PMC 4490835. PMID 26142020.
  7. Preedy, Victor R.; Burrow, Gerard N.; Watson, Ronald Ross (2009). Comprehensive Handbook of Iodine: Nutritional, Biochemical, Pathological and Therapeutic Aspects. Academic Press. p. 135. ISBN 9780080920863. Archived from the original on 12 August 2017.
  8. Sneader, Walter (2005). Drug Discovery: A History. John Wiley & Sons. p. 67. ISBN 9780471899792. Archived from the original on 26 August 2017.
  9. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  10. World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  11. "Final Rule: Changes in the Regulation of Iodine Crystals and Chemical Mixtures Containing Over 2.2 Percent Iodine". 13 September 2007. Archived from the original on 13 September 2007. Retrieved 26 August 2017.{{cite web}}: CS1 maint: bot: original URL status unknown (link)
  12. Erbil Y, Ozluk Y, Giriş M, et al. (June 2007). "Effect of lugol solution on thyroid gland blood flow and microvessel density in the patients with Graves' disease". J. Clin. Endocrinol. Metab. 92 (6): 2182–9. doi:10.1210/jc.2007-0229. PMID 17389702.
  13. Kaur S, Parr JH, Ramsay ID, et al. (May 1988). "Effect of preoperative iodine in patients with Graves' disease controlled with antithyroid drugs and thyroxine". Ann R Coll Surg Engl. 70 (3): 123–7. PMC 2498739. PMID 2457351.
  14. Han JS, John V, Blanchard SB, et al. (August 2008). "Changes in Gingival Dimensions Following Connective Tissue Grafts for Root Coverage: Comparison of Two Procedures". Journal of Periodontology. 79 (8): 1346–1354. doi:10.1902/jop.2008.070472. PMID 18672983.
  15. "JAK TO Z CZARNOBYLEM BYŁO - ZBIGNIEW JAWORSKI - Wiedza i Życie - 5/1996". archiwum.wiz.pl. Retrieved 2 November 2019.
  16. Van Den Mooter, M.; Maraite, H.; Meiresonne, L.; et al. (1 January 1987). "Comparison Between Xanthomonas campestris pv. manihotis (ISPP List 1980) and X. campestris pv. cassavae (ISPP List 1980) by Means of Phenotypic, Protein Electrophoretic, DNA Hybridization and Phytopathological Techniques". Microbiology. Microbiology Society. 133 (1): 57–71. doi:10.1099/00221287-133-1-57. ISSN 1350-0872.
  17. Lin TJ, Tanaka Y, Aznar R, Lin SC, Yamasaki Y, Hori S, Brar HK, Kirton KT, Little B (15 May 1973). "Contraceptive effect of intrauterine application of Lugol's solution". Am J Obstet Gynecol. 116 (2): 167–174. doi:10.1016/0002-9378(73)91044-2. PMID 4634105.
  18. Sreedharan et al. (June 2005). "Acute toxic gastric mucosal damage induced by Lugol's iodine spray during chromoendoscopy". Gut. 54 (6): 886–887. doi:10.1136/gut.2004.061739. PMC 1774547. PMID 15888800.{{cite journal}}: CS1 maint: uses authors parameter (link)
  19. "Material Safety Data Sheet Iodine Solution, 5% MSDS". Archived from the original on 6 December 2016. Retrieved 29 September 2016.
  20. International Programme on Chemical Safety (2009), The WHO Recommended Classification of Pesticides by Hazard (PDF), World Health Organization, p. 5, archived from the original (PDF) on 10 May 2017, retrieved 28 September 2016
  21. A Guide to The Globally Harmonized System of Classification and Labeling of Chemicals (GHS) (PDF), US Occupational Safety and Health Administration (OSHA), p. 42, archived (PDF) from the original on 3 December 2016, retrieved 28 September 2016
  22. Esciencelabs.com Archived March 3, 2014, at the Wayback Machine
  23. Rotkiewicz, Marcin; Henryk Suchar; Ryszard Kamiñski (14 January 2001). "Chernobyl: the Biggest BLUFF of the 20th Century". Polish weekly Wprost. pp. no 2. Archived from the original on 2 March 2005. Retrieved 18 June 2008.
  24. "Archived copy" (PDF). Archived from the original (PDF) on 10 September 2011. Retrieved 12 January 2010.{{cite web}}: CS1 maint: archived copy as title (link) US FDA, "Potassium Iodide as a Thyroid Blocking Agent in Radiation Emergencies," U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER); December, 2001.
  25. "Iodine." Archived 2010-08-04 at the Wayback Machine MedlinePlus.
  26. Drugs.com, "Lugol's Solution" Archived 2005-11-25 at the Wayback Machine
  27. Optimox.com, "Iodine" Archived 2006-05-06 at the Wayback Machine
  28. Jcrows.com, "Iodine" Archived 2007-01-13 at the Wayback Machine
  29. Hawkins; et al. (2005). "Change in cyanobacterial biovolume due to preservation by Lugol's Iodine". Harmful Algae. 4 (6): 1033–1043. doi:10.1016/j.hal.2005.03.001.
  30. US DEA, "Final Rule: Changes in the Regulation of Iodine Crystals and Chemical Mixtures Containing Over 2.2 Percent Iodine" Archived 2007-09-13 at the Wayback Machine (July 2, 2007) Federal Register, Volume 72, Number 126 (FR Doc E7-12736)
  31. 1 drop = 0.05 mL
  32. US FDA 1 Archived 2007-09-13 at the Wayback Machine
  33. US FDA 2 Archived 2016-03-06 at the Wayback Machine
  34. Article Archived 2016-08-03 at the Wayback Machine
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