Triclosan

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Triclosan

General
Systematic name	5-chloro-2-(2,4-dichlorophenoxy)-phenol
Other names	2,4,4'-trichloro-2'-hydroxydiphenyl ether
Molecular formula	C₁₂H₇Cl₃O₂
SMILES	C1=CC(=C(C=C1Cl)O)OC2=C(C=C(C=C2)Cl)Cl
Molar mass	289.5 g/mol
Appearance	white powdered solid
CAS number	[3380-34-5]
Properties
Density and phase	? g/cm³, ?
Solubility in water	? g/100 ml (? °C)
Melting point	55-57°C (? K)
Boiling point	120 °C (? K)
Acidity (pK_a)	4.5
Basicity (pK_b)	?
Chiral rotation [α]_D	?°
Viscosity	? cP at ? °C
Structure
Molecular shape	?
Coordination geometry	?
Crystal structure	?
Dipole moment	? D
Hazards
MSDS	External MSDS
Main hazards	Skin, eye and respiratory irritant
NFPA 704	0 0 0
Flash point	? °C
R/S statement	R: ? S: ?
RTECS number	?
Supplementary data page
Structure and properties	n, ε_r, etc.
Thermodynamic data	Phase behaviour Solid, liquid, gas
Spectral data	UV, IR, NMR, MS
Related compounds
Other anions	?
Other cations	?
Related ?	?
Related compounds	?
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.

1 Chemistry
2 Uses
3 Mechanism of action
4 Resistance concerns
5 Health concerns
6 References
7 See also
8 External links
- 8.1 Chemical

[edit] Chemistry

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, like many other phenols.

[edit] Uses

It 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) (PMID 16581155) following the successful control of MRSA outbreaks in several clinical settings. (PMID 2255283) (PMID 7677266)

Triclosan is regulated by both the U.S. Food and Drug Administration and by the European Union. In the environment, triclosan is removed during normal waste treatment processes as shown by extensive environmental studies, and any of it that remains after waste treatment quickly breaks down into other compounds in the environment. However, one study showed that triclosan was broken down into dioxins in river water, because of the presence of sunlight. (PMID 15779749).

[edit] Mechanism of action

At in-use concentrations triclosan acts as a biocide, with multiple cytoplasmic and membrane targets (PMID 15073159). However at lower concentrations 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 FabI. This binding increases the enzyme's affinity for nicotinamide adenine dinucleotide (NAD⁺). This results in the formation of a stable ternary complex of FabI-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 FabI-NAD⁺ binding, as shown in Eschericia coli and Staphylococcus aureus. (PMID 10196195)(PMID 12384334) Another way for these bacteria to gain low-level resistance to triclosan is to overexpress FabI (PMID 11418506). Some bacteria have innate resistance to triclosan, such as Pseudomonas aeruginosa, which possesses multi-drug efflux pumps that 'pump' triclosan out of the cell. (PMID 12665747) 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.

[edit] Resistance concerns

An article coauthored by Dr. Stuart Levy in the August 6, 1998 issue of Nature (PMID 9707111) 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 [1] (PMID 12957932). At least seven peer-reviewed and published studies have been conducted demonstrating that triclosan is not significantly associated with bacterial resistance, including one study coauthored by Dr. Levy, published in August of 2004 in Antimicrobial Agents and Chemotherapy (PMID 15273108).

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. (PMID 16922622)

[edit] Health concerns

Reports have suggested that triclosan can combine with chlorine in tap water to form chloroform gas (PMID 15926568), which the U.S. EPA 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 (PMID 15926568). 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.^[1] 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 is used in many common household products including Clearasil Daily Face Wash, Dentyl mouthwash, the Colgate Total range, Pepsodent, 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.

[edit] References

^ Nik Veldhoen, Rachel C. Skirrow, Heather Osachoff, Heidi Wigmore, David J. Clapson, Mark P. Gunderson, Graham Van Aggelen and Caren C. Helbing (December 2006). "The bactericidal agent triclosan modulates thyroid hormone-associated gene expression and disrupts postembryonic anuran development". Aquatic Toxicology 80 (3): 217–227.