Triclosan

Chembox new
ImageFile=Triclosan.svg
ImageSize=
ImageFile1=Triclosan-3D-vdW.pngIUPACName=5-chloro-2-(2,4-dichlorophenoxy)phenol
OtherNames= 2,4,4'-trichloro-2'-hydroxydiphenyl ether, 5-chloro-(2,4-dichlorophenoxy)phenol, trichloro-2'-hydroxydiphenyl ether, CH-3565, Lexol 300, Irgasan DP 300
Section1= Chembox Identifiers
CASNo=3380-34-5
PubChem=5564
SMILES=C1=CC(=C(C=C1Cl)O)OC2=C(C=C(C=C2)Cl)Cl
Section2= Chembox Properties
Formula=C₁₂H₇Cl₃O₂
MolarMass=289.541
Appearance=
Density=
MeltingPt=55-57 °C
BoilingPt=120 °C
Solubility=
Section3= Chembox Hazards
MainHazards=
FlashPt=
Autoignition=

Triclosan (IUPAC name: 5-chloro-2-(2,4-dichlorophenoxy)phenol) is a potent wide spectrum antibacterial and antifungal agent.

Chemical structure and properties

This organic compound is a white powdered solid with a slight aromatic/phenolic odor. It is a chlorinated aromatic compound which has functional groups representative of both ethers and phenols. Phenols often show anti-bacterial properties. Triclosan is only slightly soluble in water, but soluble in ethanol, diethyl ether, and stronger basic solutions such as 1 M sodium hydroxide, Triclosan can be made from the partial oxidation of benzene or benzoic acid, by the cumene process, or by the Raschig process. It can also be found as a product of coal oxidation.Fact|Nov2007|date=November 2007

Uses

Triclosan is found in soaps (0.15-0.30%), deodorants, toothpastes, shaving creams, mouth washes, and cleaning supplies and is infused in an increasing number of consumer products, such as kitchen utensils, toys, bedding, socks, trash bags, and some Microban treatments. Triclosan has been shown to be effective in reducing and controlling bacterial contamination on the hands and on treated products. More recently, showering or bathing with 2% triclosan has become a recommended regimen for the decolonization of patients whose skin is carrying methicillin resistant "Staphylococcus aureus" (MRSA)cite journal |author=Coia JE, Duckworth GJ, Edwards DI, "et al" |title=Guidelines for the control and prevention of meticillin-resistant Staphylococcus aureus (MRSA) in healthcare facilities |journal=J. Hosp. Infect. |volume=63 Suppl 1 |issue= |pages=S1–44 |year=2006 |pmid=16581155 |doi=10.1016/j.jhin.2006.01.001] following the successful control of MRSA outbreaks in several clinical settings.cite journal |author=Brady LM, Thomson M, Palmer MA, Harkness JL |title=Successful control of endemic MRSA in a cardiothoracic surgical unit |journal=Med. J. Aust. |volume=152 |issue=5 |pages=240–5 |year=1990 |pmid=2255283 |doi=] cite journal |author=Zafar AB, Butler RC, Reese DJ, Gaydos LA, Mennonna PA |title=Use of 0.3% triclosan (Bacti-Stat) to eradicate an outbreak of methicillin-resistant Staphylococcus aureus in a neonatal nursery |journal=American journal of infection control |volume=23 |issue=3 |pages=200–8 |year=1995 |pmid=7677266|doi=10.1016/0196-6553(95)90042-X]

Triclosan is regulated by both the U.S. Food and Drug Administration, the Environmental Protection Agency, and the European Union. During wastewater treatment, a portion of triclosan is degraded while the remaining adsorbs to sewage sludge or exits the plant in wastewater effluent.cite journal |author=Singer H, Muller S, Tixier C, Pillonel L. |title=Triclosan: occurrence and fate of a widely used biocide in the aquatic environment: field measurements in wastewater treatment plants, surface waters, and lake sediments. |journal=Environ Sci Technol. |volume=36 |issue=23 |pages=4998–5004 |year=2002 |pmid=12523412 |doi=] cite journal |author=Heidler J, Halden RU. |title=Mass balance assessment of triclosan removal during conventional sewage treatment.|journal=Chemosphere |volume=66 |issue=2 |pages=362–369 |year=2007 |pmid=16766013|doi=10.1016/j.chemosphere.2006.04.066] In the environment, triclosan may be degraded by microorganisms or react with sunlight forming other compounds which may include chlorophenols and dioxin, or it may adsorb to particles that settle out of the water column and form sediment.cite journal |author=Singer H, Muller S, Tixier C, Pillonel L. |title=Triclosan: occurrence and fate of a widely used biocide in the aquatic environment: field measurements in wastewater treatment plants, surface waters, and lake sediments. |journal=Environ Sci Technol. |volume=36 |issue=23 |pages=4998–5004 |year=2002 |pmid=12523412 |doi=] cite journal |author=Latch DE, Packer JL, Stender BL, VanOverbeke J, Arnold WA, McNeill K |title=Aqueous photochemistry of triclosan: formation of 2,4-dichlorophenol, 2,8-dichlorodibenzo-p-dioxin, and oligomerization products |journal=Environ. Toxicol. Chem. |volume=24 |issue=3 |pages=517–25 |year=2005 |pmid=15779749|doi=10.1897/04-243R.1] Triclosan was found in Greifensee sediment that was over 30 years old, suggesting that triclosan is degraded or removed slowly in sediment.cite journal |author=Singer H, Muller S, Tixier C, Pillonel L. |title=Triclosan: occurrence and fate of a widely used biocide in the aquatic environment: field measurements in wastewater treatment plants, surface waters, and lake sediments. |journal=Environ Sci Technol. |volume=36 |issue=23 |pages=4998–5004 |year=2002 |pmid=12523412 |doi=]

Mechanism of action

At in-use concentrations, triclosan acts as a biocide, with multiple cytoplasmic and membrane targets.cite journal |author=Russell AD |title=Whither triclosan? |journal=J. Antimicrob. Chemother. |volume=53 |issue=5 |pages=693–5 |year=2004 |pmid=15073159 |doi=10.1093/jac/dkh171] At lower concentrations, however, triclosan appears bacteriostatic and is seen to target bacteria mainly by inhibiting fatty acid synthesis. Triclosan binds to bacterial enoyl-acyl carrier protein reductase enzyme (ENR), 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 acid is necessary for reproducing and building cell membranes. Humans do not have an ENR enzyme, and thus are not affected. Some bacterial species can develop low-level resistance to triclosan due to FabI mutations which decrease triclosan's effect on ENR-NAD⁺ binding, as shown in "Escherichia coli" and "Staphylococcus aureus".cite journal |author=Heath RJ, Rubin JR, Holland DR, Zhang E, Snow ME, Rock CO |title=Mechanism of triclosan inhibition of bacterial fatty acid synthesis |journal=J. Biol. Chem. |volume=274 |issue=16 |pages=11110–4 |year=1999 |pmid=10196195|doi=10.1074/jbc.274.16.11110] cite journal |author=Fan F, Yan K, Wallis NG, "et al" |title=Defining and combating the mechanisms of triclosan resistance in clinical isolates of Staphylococcus aureus |journal=Antimicrob. Agents Chemother. |volume=46 |issue=11 |pages=3343–7 |year=2002 |pmid=12384334|doi=10.1128/AAC.46.11.3343-3347.2002] Another way for these bacteria to gain low-level resistance to triclosan is to overexpress "FabI".cite journal |author=Slater-Radosti C, Van Aller G, Greenwood R, "et al" |title=Biochemical and genetic characterization of the action of triclosan on Staphylococcus aureus |journal=J. Antimicrob. Chemother. |volume=48 |issue=1 |pages=1–6 |year=2001 |pmid=11418506|doi=10.1093/jac/48.1.1] Some bacteria have innate resistance to triclosan, such as "Pseudomonas aeruginosa", which possesses multi-drug efflux pumps that 'pump' triclosan out of the cell.cite journal |author=Chuanchuen R, Karkhoff-Schweizer RR, Schweizer HP |title=High-level triclosan resistance in Pseudomonas aeruginosa is solely a result of efflux |journal=American journal of infection control |volume=31 |issue=2 |pages=124–7 |year=2003 |pmid=12665747|doi=10.1067/mic.2003.11] Other bacteria, such as some of the "Bacillus" genus, have alternative "FabI" genes ("FabK") to which triclosan does not bind and hence are less susceptible.

Formation of dioxin in surface water

The use of triclosan in household anti-bacterial products introduces the chemical to surface waters where it can form dioxins. The dioxin compound that formed when triclosan degraded in sunlight was shown in a study by Virginia Tech researchers not to be of public health concern. Dioxin is not one compound, but a family of compounds of widely ranging toxicity. Of the 210 dioxin and furan family compounds, only 17 are considered to be of public health concern. [http://www.dioxinfacts.org/dioxin_health/dioxin_rumors/triclosan.html]

Resistance concerns

An article coauthored by Dr. Stuart Levy in the August 6, 1998 issue of "Nature"cite journal |author=McMurry LM, Oethinger M, Levy SB |title=Triclosan targets lipid synthesis |journal=Nature |volume=394 |issue=6693 |pages=531–2 |year=1998 |pmid=9707111 |doi=10.1038/28970] warned that triclosan's overuse could cause resistant strains of bacteria to develop, in much the same way that antibiotic-resistant bacterial strains are emerging, based on speculation that triclosan behaved like an antibiotic. Based on this speculation, in 2003, the Sunday Herald newspaper [http://ww1.sundayherald.com/37782 reported] that some UK supermarkets and other retailers were considering phasing out products containing triclosan.

It has since been shown that the laboratory method used by Dr. Levy was not effective in predicting bacterial resistance for biocides like triclosan, based on work by Dr. Peter Gilbert in the UK, whose research is supported by Procter & Gamble [http://pubs.acs.org/subscribe/journals/esthag-w/2003/nov/science/rr_triclosan.html] .cite journal |author=McBain AJ, Bartolo RG, Catrenich CE, "et al" |title=Exposure of sink drain microcosms to triclosan: population dynamics and antimicrobial susceptibility |journal=Appl. Environ. Microbiol. |volume=69 |issue=9 |pages=5433–42 |year=2003 |pmid=12957932|doi=10.1128/AEM.69.9.5433-5442.2003] At least seven peer-reviewed and published studies have been conducted demonstrating that triclosan is not significantly associated with bacterial resistance over the short term, including one study coauthored by Dr. Levy, published in August 2004 in "Antimicrobial Agents and Chemotherapy".cite journal |author=Aiello AE, Marshall B, Levy SB, Della-Latta P, Larson E |title=Relationship between triclosan and susceptibilities of bacteria isolated from hands in the community |journal=Antimicrob. Agents Chemother. |volume=48 |issue=8 |pages=2973–9 |year=2004 |pmid=15273108 |doi=10.1128/AAC.48.8.2973-2979.2004]

Some level of triclosan resistance can occur in some microorganisms, but the larger concern is with the potential for cross-resistance or co-resistance to other antimicrobials. Studies investigating this possibility have been limited.cite journal |author=Yazdankhah SP, Scheie AA, Høiby EA, "et al" |title=Triclosan and antimicrobial resistance in bacteria: an overview |journal=Microb. Drug Resist. |volume=12 |issue=2 |pages=83–90 |year=2006 |pmid=16922622 |doi=10.1089/mdr.2006.12.83]

Health concerns

Reports have suggested that triclosan can combine with chlorine in tap water to form chloroform gas,cite journal |author=Rule KL, Ebbett VR, Vikesland PJ |title=Formation of chloroform and chlorinated organics by free-chlorine-mediated oxidation of triclosan |journal=Environ. Sci. Technol. |volume=39 |issue=9 |pages=3176–85 |year=2005 |pmid=15926568 |doi=] which the United States Environmental Protection Agency classifies as a probable human carcinogen. As a result, triclosan was the target of a UK cancer alert, even though the study showed that the amount of chloroform generated was less than amounts often present in chlorinated drinking waters.

Triclosan reacts with the free chlorine in tap water to also produce lesser amounts of other compounds, like 2,4-dichlorophenol.cite journal |author=Rule KL, Ebbett VR, Vikesland PJ |title=Formation of chloroform and chlorinated organics by free-chlorine-mediated oxidation of triclosan |journal=Environ. Sci. Technol. |volume=39 |issue=9 |pages=3176–85 |year=2005 |pmid=15926568 |doi=] Most of these intermediates convert into dioxins upon exposure to UV radiation (from the sun or other sources). Although small amounts of dioxins are produced, there is a great deal of concern over this effect because some dioxins are extremely toxic and are very potent endocrine disruptors. They are also chemically very stable, so that they are eliminated from the body very slowly (they can bioaccumulate to dangerous levels), and they persist in the environment for a very long time. However, dioxin is not one compound, but a family of compounds of widely ranging toxicity. The dioxin compound that formed when triclosan degraded in sunlight is not a dioxin of public health concern.

Triclosan is chemically somewhat similar to the dioxin class of compounds. Its production leads to small amounts of residual polychlorinated dioxins, and polychlorinated furans which are contained in small amounts, in the products that are using it.

A 2006 study concluded that low doses of triclosan act as an endocrine disruptor in the North American bullfrog. [cite journal
author = Nik Veldhoen, Rachel C. Skirrow, Heather Osachoff, Heidi Wigmore, David J. Clapson, Mark P. Gunderson, Graham Van Aggelen and Caren C. Helbing
year = 2006
month = December
title = The bactericidal agent triclosan modulates thyroid hormone-associated gene expression and disrupts postembryonic anuran development
journal = Aquatic Toxicology
volume = 80
issue = 3
pages = 217–227
url = http://www.sciencedirect.com/science/article/B6T4G-4M0S2Y9-1/2/1607f34b5f4663b9c487f0481cab2162
doi = 10.1016/j.aquatox.2006.08.010 ] The hypothesis proposed is that triclosan blocks the metabolism of thyroid hormone, because it chemically mimics thyroid hormone, and binds to the hormone receptor sites, blocking them, so that normal hormones cannot be utilized. Triclosan has also been found in both the bile of fish living downstream from waste water processing plants and in human breast milk. [cite journal
author = Adolfsson-Erici M, Pettersson M, Parkkonen J, Sturve J.
year = 2002
month = March
title = Triclosan, a commonly used bactericide found in human milk and in the aquatic environment in Sweden
journal = Chemosphere
volume = 46
issue = 9–10
pages = 1485–1489
doi = 10.1016/S0045-6535(01)00255-7 ] The negative effects of Triclosan on the environment and its questionable benefits in toothpastes [cite journal
author = Edvardsson S, Burman. L G, Adolfsson­Erici. M, Bäckman. N.
year = 2005
month = August
title = Risker och nytta med triklosan i tandkräm
journal = Tandläkartidningen
volume = 97
issue = 10
pages = 58–64
url = http://www.socialstyrelsen.se/NR/rdonlyres/712300A4-7273-4388-9E64-1F55CAF02B0D/4285/Triklosan_text.pdf] has led to the Swedish Naturskyddsföreningen to recommend not using triclosan in toothpaste. [ [http://www.snf.se/pdf/rap-triclosan.pdf Start ~ Naturskyddsföreningen ] ]

Triclosan is used in many common household products including Clearasil Daily Face Wash, Dentyl mouthwash, Dawn, the Colgate Total range, Crest Cavity Protection, Softsoap, Dial, Right Guard deodorant, Sensodyne Total Care, Old Spice and Mentadent.

At this time, in the United States, manufacturers of products containing triclosan must say so somewhere on the label.

The ADA (American Dental Association) [http://www.ada.org/prof/resources/pubs/adanews/adanewsarticle.asp?articleid=1375 published a response] to the concerns stemming from the Virginia Tech study stating that Triclosan in toothpaste is not relevant.

In one study, recently accepted for publication in the journal Environmental Health Perspectives and made available online, Isaac Pessah, PhD, director of the U.C. Davis Children's Center for Environmental Health, looked at how triclosan may affect the brain. Pessah's test-tube study found that the chemical attached itself to special "receptor" molecules on the surface of cells. This raises calcium levels inside the cell. Cells overloaded with calcium get overexcited. In the brain, these overexcited cells may burn out neural circuits, which could lead to an imbalance that affects mental development. Some people may carry a mutated gene that makes it easier for triclosan to attach to their cells. That could make them more vulnerable to any effects triclosan may cause. [cite web |url=http://www.webmd.com/news/20080529/safety-debate-on-antibacterial-soap?page=2 |title=Safety of Antibacterial Soap Debated |accessdate=2008-03-08 |format= |work=]

Alternatives

A comprehensive analysis from the University of Oregon School of Public Health indicated that plain soaps are just as effective as consumer-grade anti-bacterial soaps with triclosan in preventing illness and removing bacteria from the hands. [cite web |url=http://www.physorg.com/news106418144.html |title=Plain soap as effective as antibacterial but without the risk |accessdate=2007-08-17 |format= |work=]

The addition of triclosan to hand soap can be seen as a convenience. The breakdown of waxes and oils with pure soap takes time, and a very quick application and wash-off of pure soap may be insufficient to remove bacteria protected by thick waxes. Triclosan is useful in that it is retained on the hands following washing as a residual skin coating, and continues to kill bacteria. [cite web |url=http://www.statenews.com/article.phtml?pk=34523 |title=The State News - www.statenews.com |accessdate=2007-08-17 |format= |work=] [cite web |url=http://fcs.tamu.edu/Health/Health_Education_Rural_Outreach/Health_Hints/2006/october06/staph.php |title=Antibiotic-Resistant "Staph" Infection in Our Communities | HealthHints |accessdate=2007-08-17 |format= |work=]

70% ethanol is highly effective in killing bacteria, and is now available in many hand cleaners.

Non-organic antibiotics and biocides are effective alternatives to triclosan, such as silver and copper ions and nanoparticles. [Kim, J.S., et al. Antimicrobial effects of silver nanoparticles. Nanomedicine: Nanotechnology, Biology & Medicine. 3(2007);95-101.] For instance, Tinosan SDC, is an alternative that uses a new molecule called Silver Dihydrogen Citrate (SDC).and it is also used in toothpastes

See also

* Chlorine
* Chloroform
* Chloroxylenol
* Dioxin
* Furan
* Hygiene hypothesis

References

External links

* [http://www.triclosan-info.com "Triclosan Information" from Ciba] – manufacturer information pages.
* [http://www.quantexlabs.com/AboutTriclosan/ABOUTTRICLOSAN.htm.htm "Triclosan and Its Impurities"]
* [http://www.beyondpesticides.org/pesticides/factsheets/Triclosan%20cited.pdf The Ubiquitous Triclosan: An Antibacterial Agent Exposed ] by Aviva Glaser, Beyond Pesticides
* [http://www.worldwatch.org/pubs/goodstuff/soap/ "Antibacterials? Here's the Rub"] – campaign site.
* [http://www.thisislondon.co.uk/news/articles/17956139?source=Evening%20Standard&ct=5 "Toothpaste cancer alert"] – Newspaper story.
* [http://pubs.acs.org/subscribe/journals/esthag-w/2005/apr/science/kb_chlorine.html "When chlorine + antimicrobials = unintended consequences"] – summary of research paper.
* [http://www.cbc.ca/marketplace/2007/01/triclosan.html "CBC Marketplace investigation into Triclosan"] – Investigative News story.