Triclosan

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Not to be confused with triclocarban.
Triclosan
Triclosan.svg
Triclosan-3D-vdW.png
Identifiers
CAS number 3380-34-5 YesY
PubChem 5564
ChemSpider 5363 YesY
UNII 4NM5039Y5X YesY
DrugBank DB08604
KEGG D06226 YesY
ChEBI CHEBI:164200 YesY
ChEMBL CHEMBL849 YesY
ATC code D08AE04,
D09AA06 (medicated dressing)
Jmol-3D images Image 1
Properties
Molecular formula C12H7Cl3O2
Molar mass 289.54 g mol−1
Appearance White solid
Density 1.49 g/cm3
Melting point 55–57 °C (131–135 °F; 328–330 K)
Boiling point 120 °C (248 °F; 393 K)
Hazards
MSDS MSDS
NFPA 704
Flammability code 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g., canola oil Health code 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g., chloroform Reactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g., liquid nitrogen Special hazards (white): no codeNFPA 704 four-colored diamond
Flash point 162.2 °C (324.0 °F; 435.3 K)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 YesY (verify) (what is: YesY/N?)
Infobox references

Triclosan, similar in its uses and mechanism of action to triclocarban, is an antibacterial and antifungal agent found in consumer products, including soaps, detergents, toys and, surgical cleaning treatments. Its efficacy as an antimicrobial agent and the risk of bacterial resistance remain controversial. Additional research seeks to understand its potential effects on organisms and environmental health.

Uses[edit]

Triclosan was used as a hospital scrub in the 1970s. Since then, it has expanded commercially and is now prevalent in soaps (0.10-1.00%), shampoos, deodorants, toothpastes, mouth washes and cleaning supplies.[1] It is part of consumer products, including kitchen utensils, toys, bedding, socks and trash bags.[2][3]

In healthcare, triclosan is used in surgical scrubs and hand washes.[4] Use in surgical units is effective with a minimum contact time of approximately two minutes.[5][6] More recently, showering with 2% triclosan has become a recommended regimen in surgical units for the decolonization of patients whose skin carries methicillin-resistant Staphylococcus aureus (MRSA).[7]

Triclosan has been employed as a selective agent in molecular cloning. A bacterial host transformed by a plasmid harboring a triclosan resistant mutant FabI gene (mFabI) as a selectable marker can grow in presence of high dose of triclosan in growth media.[8]

Chemical structure and properties[edit]

This organic compound is a white powdered solid with a slight aromatic, phenolic odor. Categorized as a polychloro phenoxy phenol, triclosan is a chlorinated aromatic compound that has functional groups representative of both ethers and phenols. Phenols often demonstrate antibacterial properties. Triclosan is soluble in ethanol, methanol, diethyl ether, and strongly basic solutions such as a 1M sodium hydroxide solution, but only slightly soluble in water. Triclosan can be synthesized from 2,4-dichlorophenol.

Synthesis[edit]

Under a reflux process, 2,4,4'-trichloro-2'-methoxydiphenyl ether is treated with aluminium chloride.[9]

Triclosan can be synthesized through a three-step process starting with 1-(2-hydroxyethyl)pyrrolidin-2-one. The 1-(2-hydroxyethyl)pyrrolidin-2-one is dehydrated with either zinc or calcium oxide into 1-vinylpyrrolidin-2-one.[10] Then, 1-vinylpyrrolidin-2-one can be reacted with 5-chloro-2-(2,4-dichlorophenoxy)phenyl acrylate in n-heptane to form triclosan.[11]

Mechanism of action[edit]

At high concentrations, triclosan acts as a biocide with multiple cytoplasmic and membrane targets.[12] However, at the lower concentrations seen in commercial products, triclosan appears bacteriostatic, and it targets bacteria primarily by inhibiting fatty acid synthesis.

Triclosan binds to bacterial enoyl-acyl carrier protein reductase (ENR) enzyme, which is encoded by the gene FabI. This binding increases the enzyme's affinity for nicotinamide adenine dinucleotide (NAD+). This results in the formation of a stable, ternary complex of ENR-NAD+-triclosan, which is unable to participate in fatty acid synthesis. Fatty acids are necessary for building and reproducing cell membranes. Humans do not have an ENR enzyme and thus are not affected.

Effectiveness[edit]

Some studies show that antimicrobial hand soaps containing triclosan provide a slightly greater bacterial reduction on the hands compared to plain soap, but other studies show no difference.[13] In addition, researchers at Dial found that the transfer of bacteria to objects was reduced following washing with antimicrobial hand soap containing triclosan compared to regular soap.[14] According to the FDA, antimicrobial soaps containing triclosan have not been shown to possess additional benefits over conventional soap and water.[15]

Health concerns[edit]

According to the United States Food and Drug Administration (FDA) no evidence indicates that triclosan in personal care products provides extra benefits to health beyond its anti-gingivitis effect in toothpaste.[16] Triclosan safety is under review by the FDA[16] and Health Canada.[17] A systematic review of randomized controlled trials found that triclosan-containing toothpastes are marginally beneficial in reduction of tooth cavities and reduce dental plaque, gingival inflammation, and gingival bleeding.[18]

Allergy[edit]

Triclosan has been associated with a higher risk of food allergy.[19] This may be because exposure to bacteria reduces allergies, as predicted by the hygiene hypothesis and not toxicology of the triclosan itself. This would also occur with chlorhexidine gluconate and PCMX, among other antibacterial agents.[20][21] Other studies have linked triclosan to allergic contact dermatitis in some individuals.[22][23]

By-products[edit]

Triclosan can react with the free chlorine in tap water to produce lesser amounts of other compounds, such as 2,4-dichlorophenol. Some of these intermediates convert into dioxins upon exposure to UV radiation (from the sun or other sources).[24] Although only small amounts of dioxins are produced, some dioxins are extremely toxic and are very potent endocrine disruptors. Dioxins are also chemically stable, so that they are eliminated from the body slowly (they can bioaccumulate to dangerous levels), and they persist in the environment.[25] The dioxins that can form from triclosan are not considered to be congeners of toxicologic concern for mammals, birds and fish.[26][27]

The United States Pharmacopeia formulary has published a monograph for triclosan that sets purity standards.[28]

Endocrine disruption[edit]

Triclosan has been shown to bind to both human estrogen and androgen receptors in vitro, raising concerns about its potential for developmental and reproductive effects, and for potential cancer risks. One of three studies conducted in rats showed an effect on reproductive behavior and one of four studies conducted in rats showed estrogenic effects. Two other studies found that triclosan can amplify the effects of estrogen in vivo. These studies were performed at triclosan exposures that are several orders of magnitude greater than would be encountered through environmental exposure or use of triclosan containing products.[29]

In rats, exposure to very high levels of triclosan has been associated with lower levels of thyroid hormone and testosterone. Specifically, triclosan decreases circulating levels of thyroxine hormone (T4) by increasing glucuronidase enzyme activity, which catabolizes T4 and other thyroid hormones.[29][30]

Triclosan has been found both in the bile of fish living downstream from wastewater processing facilities and in human milk.[31] The adverse effects of triclosan on the environment[32] have led the Swedish Naturskyddsföreningen to recommend avoiding triclosan in toothpaste.[33]

Environmental concerns[edit]

Treatment and disposal[edit]

The duration of triclosan in personal product use is relatively short. Upon disposal, triclosan is sent to municipal wastewater treatment plants, where about 97-98% of triclosan is removed.[34] Studies show that substantial quantities of triclosan (170,000 – 970,000 kg/yr) can break through wastewater treatment plants and damage algae on surface waters.[34] In a study on effluent from wastewater treatment facilities, approximately 75% of triclocarban was present in sludge.[35] This poses a potential environmental and ecological hazard, particularly for aquatic systems. The volume of triclosan re-entering the environment in sewage sludge after initial successful capture from wastewater is 44,000 ± 60,000 kg/yr.[34] Triclosan can attach to other substances suspended in aquatic environments, which potentially endangers marine organisms and may lead to further bioaccumulation.[36] Ozone is considered to be an effective tool for removing triclosan during sewage treatment. As little triclosan is released through plastic and textile household consumer products, these are not considered to be major sources of triclosan contamination.[36]

During wastewater treatment, a portion of triclosan is degraded, while the remaining adsorbs to sewage sludge or exits the plant as effluent.[37][38] In the environment, triclosan may be degraded by microorganisms or react with sunlight, forming other compounds, which include chlorophenols and dioxins

Bioaccumulation[edit]

While studies using semi-permeable membrane devices have found that triclosan does not strongly bioaccumulate, methyl-triclosan is comparatively more stable and lipophilic and thus poses a higher risk of bioaccumulation. The ability of triclosan to bioaccumulate is affected by its ionization state in different environmental conditions. At a higher pH, triclosan is expected to bioaccumulate more significantly, while at a lower pH, methyl-triclosan is much more likely to bioaccumulate.[39] In humans, triclosan does not bioaccumulate as it is rapidly metabolized and excreted.[40]

Ecotoxicity[edit]

Triclosan is toxic to aquatic bacteria at levels found in the environment. It is highly toxic to various types of algae and has the potential to affect the structure of algal commmunities, particularly immediately downstream of effluents from wastewater treatment facilities that treat household wastewaters.[41] Triclosan has been observed in multiple organisms, including algae aquatic blackworms, fish and dolphins. It has also been found in earth dwelling species including earth worms and species higher up the food chain.[34]

Resistance concerns[edit]

Concern pertains to the potential for cross-resistance or co-resistance to other antimicrobials. Studies investigating this possibility have been limited.[42]

The European Commission Scientific Committee on Consumer Safety (SCCS) concludes that to date, no evidence exists to suggest that using triclosan leads to an increase in antibiotic resistance. However, it is difficult to say that triclosan exposure never leads to microbial resistance, as there is too much conflicting information to make a full risk analysis.[43]

Alternatives[edit]

A comprehensive analysis from the University of Michigan School of Public Health indicated that plain soaps are just as effective as consumer-grade antibacterial soaps with triclosan in preventing illness and removing bacteria from the hands.[44]

Nonorganic antibiotics and organic biocides are effective alternatives to triclosan, such as silver and copper ions and nanoparticles.[45]

Policy[edit]

The U.S. Food and Drug Administration, the Environmental Protection Agency, and the European Union[dubious ] are regulatory bodies for triclosan. In the United States, manufacturers of products containing triclosan must indicate its presence on the label. In Europe, triclosan is regulated as a cosmetic preservative and must be listed on the label.[46] The authorization of the inclusion of triclosan as an additive for plastic production for use in food packages is a legally contentious issue, as noted in the Microban International and Microban (Europe) v Commission case.[47]

In light of the health concerns, the FDA in the 1970s reviewed the safety of triclocarban and triclosan, but took no regulatory action. In 2010, the Natural Resources Defense Council forced the FDA to review triclosan after suing them for their inaction. Since the FDA prohibited hexachlorophene, a compound similar to triclosan, Halden and others argued the FDA should also ban triclosan.[34] On December 17, 2013, the FDA issued a draft rule revoking the Generally Regarded as Safe status of triclosan as an ingredient in hand wash products, citing the need for additional studies of its potential endrocrine and developmental effects; impact on bacterial resistance; and carcinogenic potential.[48]

On May 16, 2014, Minnesota governor Mark Dayton signed a bill banning the use of triclosan in most retail consumer hygiene products sold in the state. The ban is set to take effect January 1, 2017.[49]

Current and future research[edit]

The future of TCC is unknown, but scientists are searching for more sustainable antimicrobials that maintain their antibacterial properties while also being minimally toxic to the environment, humans, and wildlife. This entails low degrees of bioaccumulation and rapid, clean biodegredation in existing wastewater treatment facilities. A lowered potential or no potential for resistance is also preferable.[50] These next generation chemicals should aim to act on a broad spectrum of microbes and pathogens while also being minimally toxic and bioaccumulating in non-target species.

Synthesis of these compounds could be improved upon by finding renewable sources for their production that lack occupational hazards.[50] Research regarding the sustainability of chemical production is currently being used to help formulate green pharmaceuticals. These same principles may be applied to the development of improved antimicrobials.[50] Development in this area would benefit both people and the environment.[50]

See also[edit]

References[edit]

  1. ^ Thompson A, Griffin P, Stuetz R, Cartmell E; Griffin; Stuetz; Cartmell (2005). "The fate and removal of triclosan during wastewater treatment". Water Environ. Res. 77 (1): 63–7. doi:10.2175/106143005X41636. JSTOR 25045839. PMID 15765937. 
  2. ^ Record in the Household Products Database of NLM
  3. ^ Crinnion, WJ; Griffin, P.; Stuetz, R.; Cartmell, E. (2005). "The CDC Fourth National Report on Human Exposure to Environmental Chemicals: what it Tells Us about our Toxic Burden and How it Assists Environmental Medicine Physicians". Water Environ. Res. 77 (1): 63–7. doi:10.2175/106143005X41636. JSTOR 25045839. PMID 15765937. 
  4. ^ Food and Drug Administration (17 June 1994). "Federal Register Notice: Tentative Final Monograph for OTC Healthcare Antiseptic Drug Products - June 17, 1994". 
  5. ^ Brady LM, Thomson M, Palmer MA, Harkness JL; Thomson; Palmer; Harkness (March 1990). "Successful control of endemic MRSA in a cardiothoracic surgical unit". Med. J. Aust. 152 (5): 240–5. PMID 2255283. 
  6. ^ Zafar AB, Butler RC, Reese DJ, Gaydos LA, Mennonna PA; Butler; Reese; Gaydos; Mennonna (June 1995). "Use of 0.3% triclosan (Bacti-Stat) to eradicate an outbreak of methicillin-resistant Staphylococcus aureus in a neonatal nursery". Am J Infect Control 23 (3): 200–8. doi:10.1016/0196-6553(95)90042-X. PMID 7677266. 
  7. ^ Coia JE, Duckworth GJ, Edwards DI et al. (May 2006). "Guidelines for the control and prevention of meticillin-resistant Staphylococcus aureus (MRSA) in healthcare facilities". J. Hosp. Infect. 63 Suppl 1: S1–44. doi:10.1016/j.jhin.2006.01.001. PMID 16581155. 
  8. ^ Jang CW, Magnuson T; Magnuson (2013). Poteete, Anthony R, ed. "A novel selection marker for efficient DNA cloning and recombineering in E. coli". PLoS ONE 8 (2): e57075. Bibcode:2013PLoSO...857075J. doi:10.1371/journal.pone.0057075. PMC 3577784. PMID 23437314. 
  9. ^ Commonwealth of Australia. Department of Health and Ageing. National Industrial Chemicals Notification and Assessment Scheme. Priority Existing Chemical Assessment Report No. 30. National Industrial Chemicals Notification and Assessment Scheme, Jan. 2009. Web. Apr. 2014.
  10. ^ US patent 6982337, "Kahn, A.P. Production of N-Vinyl Pyrrolidone" ., Apr 1, 2004.
  11. ^ US 6315987 . Nov 13, 2001.
  12. ^ Russell AD (May 2004). "Whither triclosan?". J. Antimicrob. Chemother. 53 (5): 693–5. doi:10.1093/jac/dkh171. PMID 15073159. 
  13. ^ Montville, Rebecca; Schaffner, Donald W. (1 November 2011). "A Meta-Analysis of the Published Literature on the Effectiveness of Antimicrobial Soaps". Journal of Food Protection 74 (11): 1875–1882. doi:10.4315/0362-028X.JFP-11-122. PMID 22054188. 
  14. ^ Fuls, Janice L.; Rodgers ND; et al. (April 2008). "Alternative Hand Contamination Technique To Compare the Activities of Antimicrobial and Nonantimicrobial Soaps under Different Test Conditions". Applied and Environmental Microbiology 74 (12): 3739–3744. doi:10.1128/AEM.02405-07. PMC 2446551. PMID 18441107. 
  15. ^ "Triclosan: What Consumers Should Know". Fda.gov. 2013-12-16. Retrieved 2014-07-15. 
  16. ^ a b "Triclosan: What Consumers Should Know". U S Food and Drug Administration. 8 April 2010. Retrieved 13 April 2010. 
  17. ^ "Toxic chemical monitoring program gets $500M". CBC. 4 October 2011. 
  18. ^ Philip Riley and Thomas Lamont. (December 2013). "Triclosan/copolymer containing toothpastes for oral health". Cochrane Database of Systematic Reviews 12 (CD010514): CD010514. doi:10.1002/14651858.CD010514.pub2. PMID 24310847. 
  19. ^ Sicherer, SH; Leung, DY (January 2013). "Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2012". Journal of Allergy and Clinical Immunology 131 (1): 55–66. doi:10.1016/j.jaci.2012.11.007. PMID 23199604. 
  20. ^ Clayton EM, Todd M, Dowd JB, Aiello AE; Todd; Dowd; Aiello (March 2011). "The impact of bisphenol A and triclosan on immune parameters in the U.S. population, NHANES 2003-2006". Environ. Health Perspect. 119 (3): 390–6. doi:10.1289/ehp.1002883. PMC 3060004. PMID 21062687. Lay summaryScienceDaily (Nov 30, 2010). 
  21. ^ "New Questions Raised On Chemicals In Soaps, Plastics : Shots - Health News Blog : NPR". npr.org. Retrieved 2010-11-30. 
  22. ^ Bhutani T, Jacob SE; Jacob (May 2009). "Triclosan: a potential allergen in suture-line allergic contact dermatitis". Dermatol Surg 35 (5): 888–9. doi:10.1111/j.1524-4725.2009.01151.x. PMID 19389086. 
  23. ^ Campbell L, Zirwas MJ; Zirwas (December 2006). "Triclosan". Dermatitis 17 (4): 204–7. doi:10.2310/6620.2006.06014. PMID 17150172. 
  24. ^ Bedoux, Gilles; Roig, Benoit; Thomas, Olivier; Dupont, Virginie; Le Bot, Barbara (2011). "Occurrence and toxicity of antimicrobial triclosan and by-products in the environment - Springer". Environmental Science and Pollution Research 19 (4): 1044–65. doi:10.1007/s11356-011-0632-z. PMID 22057832. 
  25. ^ "Dioxins and Furans | Persistent Bioaccumulative and Toxic (PBT) Chemical Program | US EPA". Epa.gov. 2006-06-28. Retrieved 2014-07-15. 
  26. ^ "Environmental Protection Agency". Docket. 27 March 2013. 
  27. ^ "Consultation on assessment of the health risk of dioxins; re-evaluation of the tolerable daily intake (TDI): Executive Summary". Food Additives and Contaminants 17 (4): 223–240. 2000. doi:10.1080/713810655. PMID 10912238. 
  28. ^ US Pharmacopoeia National Formulary. United States Pharmacopeial. 2012. ISBN 1936424126. 
  29. ^ a b Witorsch RJ (July 2014). "Critical analysis of endocrine disruptive activity of triclosan and its relevance to human exposure through the use of personal care products". Crit. Rev. Toxicol. 44 (6): 535–55. doi:10.3109/10408444.2014.910754. PMID 24897554. 
  30. ^ Crofton, Kevin M., et al. "Short-term in vivo exposure to the water contaminant triclosan: Evidence for disruption of thyroxine." Environmental Toxicology and Pharmacology 24.2 (2007): 194-197.
  31. ^ Adolfsson-Erici M, Pettersson M, Parkkonen J, Sturve J; Pettersson; Parkkonen; Sturve (March 2002). "Triclosan, a commonly used bactericide found in human milk and in the aquatic environment in Sweden". Chemosphere 46 (9–10): 1485–9. doi:10.1016/S0045-6535(01)00255-7. PMID 12002480. 
  32. ^ Edvardsson S, Burman LG, Adolfsson-Erici M, Bäckman N. "Risker och nytta med triklosan i tandkräm" [Risks and benefits of triclosan in toothpaste]. Tandläkartidningen (in German) 97 (10): 58–64. 
  33. ^ Start ~ Naturskyddsföreningen
  34. ^ a b c d e Halden, Rolf U. (2014). "On the Need and Speed of Regulating Triclosan and Triclocarban in the United States". Environmental Science & Technology 48 (7): 3603. doi:10.1021/es500495p. 
  35. ^ Clarke, Bradley O.; Smith, Stephen R. (2011). "Review of 'emerging'organic contaminants in biosolids and assessment of international research priorities for the agricultural use of biosolids". Environment International 37 (1): 226–247. doi:10.1016/j.envint.2010.06.004. PMID 20797791.  More than one of |pages= and |pp= specified (help)
  36. ^ a b "Triclosan Facts." EPA. Environmental Protection Agency, Web. 17 Feb. 2014.
  37. ^ Singer H, Müller S, Tixier C, Pillonel L; Müller; Tixier; Pillonel (December 2002). "Triclosan: occurrence and fate of a widely used biocide in the aquatic environment: field measurements in wastewater treatment plants, surface waters, and lake sediments". Environ. Sci. Technol. 36 (23): 4998–5004. Bibcode:2002EnST...36.4998S. doi:10.1021/es025750i. PMID 12523412. 
  38. ^ Heidler, J; Halden, RU (January 2007). "Mass balance assessment of triclosan removal during conventional sewage treatment". Chemosphere 66 (2): 362–9. doi:10.1016/j.chemosphere.2006.04.066. PMID 16766013. 
  39. ^ Brausch, John, and Gary Rand. "A review of personal care products in the aquatic environment: Environmental concentrations and toxicity" Chemosphere 82.11 (2011): 1518-1532. ScienceDirect. Web. 17 Feb. 2014.
  40. ^ "Triclosan". Retrieved 2014-09-22. 
  41. ^ "Estimates Of Exposures And Risks To Aquatic Organisms From Releases Of Triclosan To Surface Water As A Result Of Uses Under EPA’S Jurisdiction". Retrieved 2014-09-22. 
  42. ^ Yazdankhah SP, Scheie AA, Høiby EA et al. (2006). "Triclosan and antimicrobial resistance in bacteria: an overview". Microb. Drug Resist. 12 (2): 83–90. doi:10.1089/mdr.2006.12.83. PMID 16922622. 
  43. ^ Triclosan and Antibiotics resistance summary by GreenFacts of an opinion by the European Commission Scientific Committee on Consumer Safety (March 2010)
  44. ^ "Plain soap as effective as antibacterial but without the risk". Retrieved 2007-08-17. 
  45. ^ Kim JS, Kuk E, Yu KN et al. (March 2007). "Antimicrobial effects of silver nanoparticles". Nanomedicine 3 (1): 95–101. doi:10.1016/j.nano.2006.12.001. PMID 17379174. 
  46. ^ "REGULATION (EC) No 1223 /2009 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 30 November 2009 on cosmetic products". Official Journal of the European Union. 2009. 
  47. ^ COMMISSION DECISION of 19 March 2010 concerning the non-inclusion of 2,4,4’-trichloro-2’-hydroxydiphenyl ether in the Union list of additives which may be used in the manufacture of plastic materials and articles intended to come into contact with foodstuffs under Directive 2002/72/EC 23.3.2010 Official Journal of the European Union
  48. ^ "Federal Register". Retrieved 2014-09-22. 
  49. ^ STEVE KARNOWSKI (2014-05-20). "Minnesota Becomes First State To Ban Antibacterial Chemical Triclosan From Soaps". Huffingtonpost.com. Retrieved 2014-07-15. 
  50. ^ a b c d Halden, Rolf U. "On the Need and Speed of Regulating Triclosan and Triclocarban in the United States." Environmental science & technology (2014). http://pubs.acs.org/doi/abs/10.1021/es500495p

External links[edit]