Identification

Name
Triclocarban
Accession Number
DB11155
Type
Small Molecule
Groups
Approved
Description

Triclocarban, with the chemical formula C13H9Cl3N2O [10] is an antibacterial agent that is particularly effective against Gram-positive bacteria such as Staphylococcus aureus. It is a bacteriostatic compound that has been found in antibacterial soaps and other personal care products. In 2017, the US FDA prohibited the marketing of over-the-counter (OTC) consumer antiseptic wash products containing triclocarban due to negative health effects such as bacterial resistance or hormonal effects [7], [8].

Structure
Thumb
Synonyms
  • 1-(3',4'-dichlorophenyl)-3-(4'-chlorophenyl)urea
  • 3,4,4'-trichloro carbanilide
  • 3,4,4'-trichlorocarbanilide
  • 3,4,4'-trichlorodiphenylurea
  • N-(4-chlorophenyl)-N'-(3,4-dichlorophenyl)urea
  • Triclocarban
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
1st Date antibacterial Deodorant (Gold)Soap0.3 g/100gTopicalGuilin Share Friend Daily Use Chemical Co.,Ltd2015-08-01Not applicableUs
1st Date antibacterial Deodorant (Green)Soap0.3 g/100gTopicalGuilin Share Friend Daily Use Chemical Co.,Ltd2015-08-01Not applicableUs
1st Date antibacterial Deodorant (White)Soap0.3 g/100gTopicalGuilin Share Friend Daily Use Chemical Co.,Ltd2015-08-01Not applicableUs
a.c.care Bees Foam CleanserCream459 mg/150mLTopicalDong Sung Pharm. Co., Ltd.2014-09-232015-11-30Us
a.c.care Bees Foam Cleanser Troubled Skin Care 2 pcs SetCream153 mg/50mLTopicalDong Sung Pharm. Co., Ltd.2014-12-042015-11-30Us
a.c.care Bees Troubled Skin Care 2 pcs SetCream153 mg/50mLTopicalDong Sung Pharm. Co., Ltd.2014-12-042014-12-08Us
AmerFresh Antibacterial DeodorantSoap15 mg/1gTopicalAmercare Products, Inc.2015-11-112017-08-31Us
Amerfresh Antibacterial DeodorantSoap1.5 g/100gTopicalAmercare Products, Inc.2010-09-032020-05-01Us
Antibacterial BeautySoap.1 g/100gTopicalKareway Product, Inc.2011-09-07Not applicableUs
Antibacterial DeodorantSoap0.3 g/100gCutaneousDolgencorp2015-09-292017-10-29Us
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Zarina Medicated Antiseptic SoapTriclocarban (0.4 %) + Triclosan (0.1 %)SoapTopicalFairtrade International Co. Ltd.Not applicableNot applicableCanada
International/Other Brands
Cutisan / Nobacter / Solubacter
Categories
UNII
BGG1Y1ED0Y
CAS number
101-20-2
Weight
Average: 315.58
Monoisotopic: 313.978046
Chemical Formula
C13H9Cl3N2O
InChI Key
ICUTUKXCWQYESQ-UHFFFAOYSA-N
InChI
InChI=1S/C13H9Cl3N2O/c14-8-1-3-9(4-2-8)17-13(19)18-10-5-6-11(15)12(16)7-10/h1-7H,(H2,17,18,19)
IUPAC Name
3-(4-chlorophenyl)-1-(3,4-dichlorophenyl)urea
SMILES
ClC1=CC=C(NC(=O)NC2=CC(Cl)=C(Cl)C=C2)C=C1

Pharmacology

Indication

Triclocarban (TCC), or 3,4,4'-trichlorocarbanilide, is an antibacterial agent used in bar and liquid soaps and body washes [17].

Pharmacodynamics

The antimicrobial mechanism underlying the bacteriostatic and bactericidal effects of triclocarban is believed to be an unspecific adsorption to cell membranes and interruption of their function. As a result, the growth of gram-positive as well as gram-negative bacteria is inhibited [15].

Mechanism of action

Triclocarban is a triclosan analog with an antibacterial activity. Triclocarban exerts its effect by inhibiting the activity of enoyl-(acyl-carrier protein) (ACP) reductase, which is ubiquitously distributed in bacteria, fungi and various plants. ACP reductase catalyzes the last step in each cycle of fatty acid elongation in the type II fatty acid synthase systems. As a result, this agent interrupts cell membrane synthesis and leads to bacterial growth inhibition [17].

TargetActionsOrganism
AEnoyl-[acyl-carrier-protein] reductase [NADPH] FabI
antagonist
Staphylococcus aureus (strain MRSA252)
Absorption

A human exposure study in a small group of subjects demonstrated that a portion of the TCC present in bar soaps is absorbed through the skin and is excreted in urine as N-glucuronides [2].

Because they are produced and used in large quantities in various products, they are absorbed into the human body of the general population [13].

The absorption of triclocarban during a human pharmacokinetic study was estimated at 0.6% of the 70 + or - 15 mg of triclocarban in the soap used. The triclocarban-N-glucuronide urine concentration varied considerably among the study subjects, and continuous daily use of the soap led to steady-state levels of excretion [17].

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Blood levels after parenteral injection are low and comparison of the radioactivity and chemical determinations suggest rapid metabolism of the Triclocarban [17].

Human metabolism of TCC involves direct glucuronidation to form N- and N'- glucuronides as well as ring hydroxylation to 2'-hydroxy-TCC and 6-hydroxy-TCC, which are further metabolized to sulfate and glucuronide conjugates. In human subjects given a single oral dose of TCC, 27% of the dose was excreted in the urine within 80 hours. About 70% of the administered dose was excreted in the feces within 5 days [17].

The major urinary metabolites were N-glucuronides (average levels, 30 ng/mL) and a major plasma metabolite was the sulfate conjugate of 2'-OH-TCC (levels ranged from 0-20 ng/mL [17].

The maximum plasma level occurred 2.8 hr after dosing and was 3.7 nmol-equivalents of TCC per g of plasma (approximately 1.2 ppm). Biotransformation of TCC was rapid but did not appear to involve splitting of the basic TCC structure. The major plasma metabolites were N- and N'-glucuronides of TCC which were eliminated with half-life approximately 2 hr to the urine and 2'-hydroxy-TCC sulfate and 6-hydroxy-TCC sulfate (the o-hydroxy-TCC sulfates) which were removed with half life approximately 20 hr (presumably into the bile) [17].

Route of elimination

The metabolism of (14)C-TCC (3,4,4'-trichlorocarbanilide) has been investigated in humans following oral exposure to 2.2 mumol/kg. Fecal elimination (70% of dose) was complete at the 120 hour point after administration and the urinary excretion (27% of dose) was complete after 80 hours post-administration [17].

Urinary glucuronides appear to be valuable biomarkers of triclocarban exposure [2].

Half life

10 hours [14]

Clearance

After a pharmacokinetic study in man, radioactivity was rapidly cleared from blood after intravenous administrations of (14)C-triclocarban in propylene glycol with a blood clearance half-life measured to be 8.6 hours [17].

Toxicity

Ld50 of 2100 mg/kg in mice [9].

There has been concern voiced over the endocrine effect of triclocarban ande, in particular, on estrogen [4], [5],[6],[16].

One study determined that triclocarban by itself stimulates AroB (brain aromatase) gene expression only slightly, but TCC strongly enhances the overexpression of AroB that is induced by exogenous estrogen. TCC has the potential to elevate levels of aromatase enzymes and, thereby, levels of endogenous estrogens in the developing brain [17]. The effects of triclocarban on the endocrine system are presently not fully elucidated.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Schebb NH, Muvvala JB, Morin D, Buckpitt AR, Hammock BD, Rice RH: Metabolic activation of the antibacterial agent triclocarban by cytochrome P450 1A1 yielding glutathione adducts. Drug Metab Dispos. 2014 Jul;42(7):1098-102. doi: 10.1124/dmd.114.058206. Epub 2014 Apr 14. [PubMed:24733789]
  2. Schebb NH, Inceoglu B, Ahn KC, Morisseau C, Gee SJ, Hammock BD: Investigation of human exposure to triclocarban after showering and preliminary evaluation of its biological effects. Environ Sci Technol. 2011 Apr 1;45(7):3109-15. doi: 10.1021/es103650m. Epub 2011 Mar 7. [PubMed:21381656]
  3. Schebb NH, Franze B, Maul R, Ranganathan A, Hammock BD: In vitro glucuronidation of the antibacterial triclocarban and its oxidative metabolites. Drug Metab Dispos. 2012 Jan;40(1):25-31. doi: 10.1124/dmd.111.042283. Epub 2011 Sep 27. [PubMed:21953915]
  4. Kennedy RC, Menn FM, Healy L, Fecteau KA, Hu P, Bae J, Gee NA, Lasley BL, Zhao L, Chen J: Early life triclocarban exposure during lactation affects neonate rat survival. Reprod Sci. 2015 Jan;22(1):75-89. doi: 10.1177/1933719114532844. Epub 2014 May 6. [PubMed:24803507]
  5. Chen J, Ahn KC, Gee NA, Ahmed MI, Duleba AJ, Zhao L, Gee SJ, Hammock BD, Lasley BL: Triclocarban enhances testosterone action: a new type of endocrine disruptor? Endocrinology. 2008 Mar;149(3):1173-9. doi: 10.1210/en.2007-1057. Epub 2007 Nov 29. [PubMed:18048496]
  6. Huang H, Du G, Zhang W, Hu J, Wu D, Song L, Xia Y, Wang X: The in vitro estrogenic activities of triclosan and triclocarban. J Appl Toxicol. 2014 Sep;34(9):1060-7. doi: 10.1002/jat.3012. Epub 2014 Apr 16. [PubMed:24740835]
  7. FDA bans triclosan and triclocarban in consumer soaps [Link]
  8. FDA issues final rule on safety and effectiveness of antibacterial soaps [Link]
  9. Triclorcarban ToxNet [Link]
  10. European Chemicals Agency - Triclorcarban [Link]
  11. Temporal Development of Gut Microbiota in Triclocarban Exposed Pregnant and Neonatal Rats [Link]
  12. Binding mechanism of triclocarban with human serum albumin: Effect on the conformation and activity of the model transport protein [Link]
  13. Triclocarban and Triclosan Inhibit Human Aromatase via Different Mechanisms [Link]
  14. Triclocarban [Link]
  15. Investigation of human exposure, metabolism and biological effects of the antibacterial triclocarban [Link]
  16. Effects of triclocarban on the transcription of estrogen, androgen and aryl hydrocarbon receptor responsive genes in human breast cancer cells [Link]
  17. Triclocarban, PuBMED [Link]
  18. Triclocarban [CASRN 101-20-2] [File]
External Links
KEGG Drug
D06223
PubChem Compound
7547
PubChem Substance
347827924
ChemSpider
7266
BindingDB
25730
ChEBI
48347
ChEMBL
CHEMBL1076347
HET
9EG
Wikipedia
Triclocarban
AHFS Codes
  • 84:04.92 — Miscellaneous Local Anti-infectives
PDB Entries
5vl2 / 5vm0 / 5vm6
MSDS
Download (415 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingTreatmentHyperhidrosis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CreamTopical459 mg/150mL
CreamTopical153 mg/50mL
SoapTopical15 mg/1g
SoapTopical.1 g/100g
SoapCutaneous0.3 g/100g
SoapCutaneous0.16 g/100g
SoapTopical1.5 %
SoapTopical2.6 g/10g
SoapTopical1.3 g/10g
SoapTopical0.6 g/100g
SoapTopical1 %
SoapTopical1.5 mg/100mg
SoapTopical1.5 g
SoapTopical0.29 g/100g
SoapTopical1.017 g/339g
SoapTopical.339 g/113g
SoapCutaneous0.60 1/1
SoapTopical113 g/113g
SoapTopical.60 g/100g
SoapTopical6 mg/1g
SoapTopical0.3 g/100g
SoapTopical0.33 mg/100mg
SoapTopical0.744 g/99.225g
SoapCutaneous0.45 g/90g
SoapTopical1.5 g/100g
SoapTopical.67 g/86g
LiquidTopical1.5 mg/1000mL
SoapTopical4 mg/1g
LiquidTopical1.5 mL/1L
SoapTopical0.3 g/1g
SoapTopical1.356 g/113g
SoapTopical
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)491.2- 493MSDS
water solubilityInsoluble MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.0029 mg/mLALOGPS
logP5.1ALOGPS
logP4.93ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)11.42ChemAxon
pKa (Strongest Basic)-4.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area41.13 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity80.47 m3·mol-1ChemAxon
Polarizability28.19 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-9bbaca4c62706668edcb
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-9bbaca4c62706668edcb
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-7b1368df2f08ebba94cb
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-1e1a66cc3faa0105ec7f
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-327a5c91ff007c309e4a
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-1e1a66cc3faa0105ec7f
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-0900000000-68ed903c2c78b374365e
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-0900000000-fc03d43145b4d7923be8
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03fr-0900000000-b71026cd198f291dd119
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0009000000-9a158e4646b9312b78b3
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0906000000-cbc0ac99651dcf244c6c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-01t9-0900000000-45e729bb952bf46c6c81
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-1900000000-3c0b2116f600b5e42772
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-2900000000-7db83ea06645d920fc36
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-3900000000-6076de3ccc95186d3083
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0009000000-56e898564ed2199ae328
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0906000000-c0e21ba1862cfe9d1ccf
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-01t9-0900000000-7b86cd9e2961f81a1b27
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-1900000000-5eec05ea41af9b11f73f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-2900000000-72f4dd6f6e2d0e14c234
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-3900000000-cfc10b9b7896ba4ea874
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03fr-0900000000-9cec2aa3eaed3fd3db56
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-1900000000-46d8a2c85f55728c6087
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-3900000000-860e0e45f099006579fc
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03fr-0900000000-2334807b29cd171659b9
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03fr-0900000000-1b296765c6c646b3dd53
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03fr-1905000000-4bceb1887e15e32eea63

Taxonomy

Description
This compound belongs to the class of organic compounds known as dichlorobenzenes. These are compounds containing a benzene with exactly two chlorine atoms attached to it.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Halobenzenes
Direct Parent
Dichlorobenzenes
Alternative Parents
Aryl chlorides / Isoureas / Propargyl-type 1,3-dipolar organic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
1,2-dichlorobenzene / Aryl chloride / Aryl halide / Isourea / Carboximidic acid derivative / Organic 1,3-dipolar compound / Propargyl-type 1,3-dipolar organic compound / Organic nitrogen compound / Organonitrogen compound / Organochloride
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
ureas, dichlorobenzene, monochlorobenzenes (CHEBI:48347)

Targets

Kind
Protein
Organism
Staphylococcus aureus (strain MRSA252)
Pharmacological action
Yes
Actions
Antagonist
General Function
Nadp binding
Specific Function
Catalyzes the reduction of a carbon-carbon double bond in an enoyl moiety that is covalently linked to an acyl carrier protein (ACP). Involved in the elongation cycle of fatty acid which are used i...
Gene Name
fabI
Uniprot ID
Q6GI75
Uniprot Name
Enoyl-[acyl-carrier-protein] reductase [NADPH] FabI
Molecular Weight
27991.645 Da
References
  1. FDA issues final rule on safety and effectiveness of antibacterial soaps [Link]
  2. Triclocarban, PuBMED [Link]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Effects of triclocarban on the transcription of estrogen, androgen and aryl hydrocarbon receptor responsive genes in human breast cancer cells [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1B1
Uniprot ID
Q16678
Uniprot Name
Cytochrome P450 1B1
Molecular Weight
60845.33 Da
References
  1. Effects of triclocarban on the transcription of estrogen, androgen and aryl hydrocarbon receptor responsive genes in human breast cancer cells [Link]

Drug created on December 03, 2015 09:51 / Updated on December 14, 2018 17:13