triclosan

Triclosan
IUPAC name	5-chloro-2-(2,4-dichlorophenoxy)phenol
Identifiers
CAS number	3380-34-5
PubChem	5564
SMILES	C1=CC(=C(C=C1Cl)O)OC2=C(C=C(C=C2)Cl)Cl
Properties
Molecular formula	C12H7Cl3O2
Molar mass	289.541
Melting point	55-57°C
Boiling point	120 °C
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references

Triclosan (chemically 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 slightly soluble in water, but soluble in ethanol, diethyl ether, and stronger basic solutions such as 1 M sodium hydroxide, Synonyms: 2,4,4'-trichloro-2'-hydroxydiphenyl ether, 5-chloro-(2,4-dichlorophenoxy)phenol, trichloro-2'-hydroxydiphenyl ether, CH-3565, Lexol 300, Irgasan DP 200 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

Uses

Triclosan is found in soaps, deodorants, toothpastes, mouthwashes, and cleaning supplies and is infused in an increasing number of consumer products, such as kitchen utensils, toys, bedding, socks, and trash bags, sometimes as the proprietary Microban treatment. It 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 regime for the decolonization of patients whose skin is carrying methicillin resistant Staphylococcus aureus (MRSA)^[1] following the successful control of MRSA outbreaks in several clinical settings.^[2][3]

Triclosan is regulated by both the U.S. Food and Drug Administration and by 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.^[4][5] 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.^[4][6]. Triclosan was found in Lake Greifensee sediment that was over 30 years old suggesting that triclosan is degraded or removed slowly in sediment.^[4]

Mechanism of action

At in-use concentrations triclosan acts as a biocide, with multiple cytoplasmic and membrane targets.^[7] 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. ^[8][9] Another way for these bacteria to gain low-level resistance to triclosan is to overexpress FabI.^[10] Some bacteria have innate resistance to triclosan, such as Pseudomonas aeruginosa, which possesses multi-drug efflux pumps that 'pump' triclosan out of the cell.^[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.

Resistance concerns

An article coauthored by Dr. Stuart Levy in the August 6, 1998 issue of Nature^[12] warned that its 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 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 [1].^[13] 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 of 2004 in Antimicrobial Agents and Chemotherapy.^[14]

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.^[15]

Health concerns

Reports have suggested that triclosan can combine with chlorine in tap water to form chloroform gas,^[16] 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.^[16] 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 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.

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.^[17] 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 down stream from waste water processing plants and in human breast milk.^[18] The negative effects of Triclosan on the environment and its questionable benefits in toothpastes ^[19] has led to the Swedish Naturskyddsföreningen to recommend not using Triclosan in toothpaste. ^[20]

Triclosan is used in many common household products including Clearasil Daily Face Wash, Dentyl mouthwash, Dawn, the Colgate Total range, 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.

Alternatives

Although frequently used as an additive to soap, triclosan is not actually necessary in soap to kill bacteria. Soap is itself an effective microbicide due to the fact that soap breaks down oils. All bacterial cell walls are based on lipid chains, which are oil-based. The simple act of applying soap to the hands and rubbing vigorously will cause the cell walls of any bacteria on the hands to be ripped apart by the soap, disintegrating and killing any bacteria present. A comprehensive analysis from the U-M School of Public Health indicated that plain soaps are just as effective as consumer-grade anti-bacterial soaps with triclosan in preventing illness and reducing bacteria on the hands.^[21]

Soap can damage the cell walls of all animal cells and can also kill / disintegrate human cells, but the thick layer of dead cells in the epidermis of the skin generally protects humans from the potentially damaging effects of soap. Repeated frequent scrubbing with soap can remove the skin oils impregnating the layer of dead skin cells, leading to dryness and flaking of the dead cell layer.

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 break down 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.^[22][23]

References

See also

• Chlorine
• Chloroform
• Chloroxylenol
• Dioxin
• Furan

External links

Positive/neutral/official

• Triclosan Information from Ciba Specialty Chemicals – manufacturer information pages.

Primary source (research)

• Triclosan and Its Impurities

Negative

• The Ubiquitous Triclosan: An Antibacterial Agent Exposed by Aviva Glaser, Beyond Pesticides
• Antibacterials? Here's the Rub – campaign site.
• Toothpaste cancer alert – Newspaper story.
• When chlorine + antimicrobials = unintended consequences – summary of research paper.
• CBC Marketplace investigation into Triclosan – Investigative News story.

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