Triclocarban (sometimes abbreviated as TCC) is an antibacterial chemical once common in, but now phased out of, personal care products like soaps and lotions. It was originally developed for the medical field. Although the mode of action is unknown, TCC can be effective in fighting infections by targeting the growth of bacteria such as Staphylococcus aureus. Additional research seeks to understand its potential for causing antibacterial resistance and its effects on organismal and environmental health.
Usage Triclocarban has been used as an antimicrobial and antifungal compound since the 1960s. It was commonly found in personal care products as an antimicrobial in soaps, lotions, deodorants, toothpaste, and plastic. As of 2005 about 80% of all antimicrobial bar soap sold in the United States contained triclocarban. In 2011 United States consumers were spending nearly 1 billion dollars annually on products containing triclocarban and triclosan. In December 2013, the Food and Drug Administration (FDA) required all companies to prove within the next year, that triclocarban is not harmful to consumers. Companies like Johnson & Johnson, Procter & Gamble, Colgate-Palmolive, and Avon began phasing out antibacterial ingredients due to health concerns. By 2016 usage of triclocarban in soaps had declined to 40%, and that September the FDA banned triclocarban, triclosan and 17 other common antibacterial chemicals by September 2017, for their failure to be proven safe, or more effective than plain soap and water.
Chemical structure and properties Triclocarban, 3-(4-chlorophenyl)-1-(3,4-dichlorophenyl)urea, is a white powder that is insoluble in water. While triclocarban has two chlorinated phenyl rings, it is structurally similar to carbanilide compounds often found in pesticides (such as diuron) and some drugs. Chlorination of ring structures is often associated with hydrophobicity, persistence in the environment, and bioaccumulation in fatty tissues of living organisms. For this reason, chlorine is also a common component of persistent organic pollutants. Triclocarban is incompatible with strong oxidizing reagents and strong bases, reaction with which could result in safety concerns such as explosion, toxicity, gas, and heat.
Synthesis of triclocarban There are two commercial routes used for the production of triclocarban, using the reaction of isocyanates with nucleophiles such as amines to form ureas:
4-chlorophenylisocyanate is reacted with 3,4-dichloroaniline 3,4-dichlorophenylisocyanate is reacted with 4-chloroaniline The purity specification in the draft USP monograph for triclocarban is: not less than 97.0% w/w. The purity of commercial production is greater, 98% w/w.
Mechanism of action
Bacteria Triclocarban is predominantly active against gram positive bacteria (bacteria with a thick peptidoglycan wall). The precise mechanism of action of triclocarban is unknown, but it is shown to be bacteriostatic, which prevents bacterial proliferation.
Humans The specific mechanism of action for triclocarban's health effects on humans, like in bacteria, is unclear. Generally, in vitro, triclocarban enhances the gene expression of other steroid hormones, including androgens, estrogens, and cortisol. It is hypothesized that the compound acts similar to cofactors or coactivators that modulate the activity of estrogen receptors and androgen receptors. Experiments show that triclocarban activates constitutive androstane receptor and estrogen receptor alpha both in vivo and in vitro and might have the potential to alter normal physiological homeostasis. Activation of these receptors amplifies gene expression and, in doing so, may be the mechanistic base of triclocarban's health impact on humans. However, further investigation is needed to determine whether triclocarban increases the activity of sex steroid hormones by binding to the receptors or by binding to and sensitizing the receptor coactivators.
Antibacterial properties Triclocarban acts to treat both initial bacterial skin and mucosal infections as well as those infections at risk for superinfection. In vitro, triclocarban has been found to be effective against various strains of staphylococcus, streptococcus, and enterococcus bacteria. It has been shown to be effective as an antibacterial even at very low levels. Triclocarban's minimum inhibitory concentration has been found to range from 0.5 to 8 mg/L for these various strains. Triclocarban is unquestionably bacteriostatic only for gram-positive bacteria such as Staphylococcus aureus, which suggests that the mechanism of triclocarban's antibacterial activity is through its destabilization of bacterial cell walls.
Resistance Exposure of organisms like fish, algae, and humans to low levels of triclocarban and other antibacterial chemicals kills weak microbes and allows the stronger, resistant strains to proliferate. As microbes share genes, an increase in resistant strains increases the probability that weak microbes acquire these resistance genes. The consequence is a new colony of drug resistant microbes. When resistant microbes are exposed to antimicrobials, they increase their expression of genes that confer this resistance. The risk of bacterial antibiotic resistance has been studied by quantitatively monitoring the abundance of the tetQ gene in wastewater microcosms. As tetQ is the most common resistance gene in the environment and encodes for ribosomal protection proteins, the amount that it expresses correlates with the amount of resistance in a microbial population. The addition of triclocarban was shown to increase the expression of this tetQ gene. TetQ gene expression in bacteria was also found to be significantly increased when multiple antimicrobials such as tetracycline, triclosan, and triclocarban were added to an experimental system at the same time. Combining these compounds affects resistance by creating a situation where co-selection (or natural selection by more than one reagent) for resistance genes occurs. The complex nature of microbial communities and the multitude of antibiotics present in aquatic environments often leads to this sort of dynamic selection event and the multiple resistance patterns seen in naturally occurring bacteria.
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