TETRACHLOROPHENOL

General Information

Mainterm	TETRACHLOROPHENOL
CAS Reg.No.(or other ID)	25167-83-3
Regnum

From www.fda.gov

Computed Descriptors

Download SDF

2D Structure
CID	21013
IUPAC Name	2,3,4,5-tetrachlorophenol
InChI	InChI=1S/C6H2Cl4O/c7-2-1-3(11)5(9)6(10)4(2)8/h1,11H
InChI Key	RULKYXXCCZZKDZ-UHFFFAOYSA-N
Canonical SMILES	C1=C(C(=C(C(=C1Cl)Cl)Cl)Cl)O
Molecular Formula	C6H2Cl4O
Wikipedia	2,3,4,5-tetrachlorophenol

From Pubchem

Computed Properties

Property Name	Property Value
Molecular Weight	231.881
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	1
Rotatable Bond Count	0
Complexity	143.0
CACTVS Substructure Key Fingerprint	A A A D c Q B g I A A H A A A A A A A A A A A A A A A A A A A A A A A w A A A A A A A A A A A B A A A A G g I A C A A A C A a A k C A w B o A A A g C A A C B C A A A C A A A g J U A A i k A G C 4 g I J i K D E h K A c A A k w B E I m A e A Q A A A A C A Q A Q C A C A Q A Q C A C A Q A Q C A A A A A A A A A = =
Topological Polar Surface Area	20.2
Monoisotopic Mass	229.886
Exact Mass	231.883
Compound Is Canonicalized	True
Formal Charge	0
Heavy Atom Count	11
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Isotope Atom Count	0
Covalently-Bonded Unit Count	1

From Pubchem

ADMET Predicted Profile --- Classification

Model	Result	Probability
Absorption
Blood-Brain Barrier	BBB+	0.9643
Human Intestinal Absorption	HIA+	0.9932
Caco-2 Permeability	Caco2+	0.8943
P-glycoprotein Substrate	Non-substrate	0.8164
P-glycoprotein Inhibitor	Non-inhibitor	0.9782
P-glycoprotein Inhibitor	Non-inhibitor	0.9941
Renal Organic Cation Transporter	Non-inhibitor	0.8694
Distribution
Subcellular localization	Mitochondria	0.8731
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.7834
CYP450 2D6 Substrate	Non-substrate	0.8320
CYP450 3A4 Substrate	Non-substrate	0.6716
CYP450 1A2 Inhibitor	Inhibitor	0.8447
CYP450 2C9 Inhibitor	Non-inhibitor	0.6560
CYP450 2D6 Inhibitor	Non-inhibitor	0.9307
CYP450 2C19 Inhibitor	Inhibitor	0.5210
CYP450 3A4 Inhibitor	Non-inhibitor	0.8866
CYP Inhibitory Promiscuity	Low CYP Inhibitory Promiscuity	0.6737
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.8043
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.9426
AMES Toxicity	Non AMES toxic	0.9306
Carcinogens	Non-carcinogens	0.7562
Fish Toxicity	High FHMT	0.9126
Tetrahymena Pyriformis Toxicity	High TPT	0.9877
Honey Bee Toxicity	High HBT	0.7919
Biodegradation	Not ready biodegradable	0.8276
Acute Oral Toxicity	III	0.8688
Carcinogenicity (Three-class)	Non-required	0.6275

From admetSAR

ADMET Predicted Profile --- Regression

Model	Value	Unit
Absorption
Aqueous solubility	-2.2778	LogS
Caco-2 Permeability	1.8233	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	2.4130	LD50, mol/kg
Fish Toxicity	0.5640	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	1.5348	pIGC50, ug/L

From admetSAR

Toxicity Profile

Route of Exposure	Inhalation ; oral ; dermal ; eye contact
Mechanism of Toxicity	Tetrachlorophenols decrease or block ATP production without blocking the electron transport chain. Thus the poisons uncouple phosphorylation from oxidation. Free energy from the electron transport chain then converts to more body heat. As body temp rises, heat-dissipating mechanisms are overcome and metabolism is speeded. More ADP and other substrates accumulate, and these substrates stimulate the electron transport chain further. The electron transport chain responds by using up more and more available oxygen (increasing oxygen demand) in an effort to produce ATP, but much of the free energy generated is liberated as still more body heat. Oxygen demand quickly overcomes oxygen supply, and energy reserves become depleted.
Metabolism	Tetrachlorophenols are rapidly absorbed and excreted following occupational exposure, which involves both the inhalation and dermal routes. Most of the 2,3,4,5-tetrachlorophenol is excreted unchanged in the urine; trichlorohydroquinone has been identified as one of its metabolites.
Toxicity Values	LD50: >2000 mg/kg (Dermal, Rabbit) LD50: 400 mg/kg/day (Oral, Mouse)
Lethal Dose	None
Carcinogenicity (IARC Classification)	Not directly listed by IARC, but related polychlorophenols are discussed, and combined exposures to polychlorophenols or to their sodium salts are classified as possibly carcinogenic to humans (Group 2B).
Minimum Risk Level	Acute Oral: 0.01 mg/kg/day (Rat) Intermediate Oral: 0.003 mg/kg/day (Rat)
Health Effects	Dermal exposure can cause corrosive skin damage. (L159)
Treatment	In case of oral exposure, dilution may enhance absorption of phenol and should be avoided, but charcoal may be administered. If methemoglobinemia occurs, administer 1 to 2 mg/kg of 1% methylene blue slowly IV in symptomatic patients. Additional doses may be required. If hypotension occurs, infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine or norepinephrine. Following inhalation exposure, move patient to fresh air. Monitor for respiratory distress, and if cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. Irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes following eye exposure. Following dermal exposure, remove phenol with undiluted polyethylene glycol 300 to 400 or isopropyl alcohol prior to washing, if readily available. Wash exposed areas twice or for at least 10 minutes with large quantities of soapy water. Water alone may be harmful.
Reference	Huq MD, Tsai NP, Gupta P, Wei LN: Regulation of retinal dehydrogenases and retinoic acid synthesis by cholesterol metabolites. EMBO J. 2006 Jul 12;25(13):3203-13. Epub 2006 Jun 8.[16763553 ]

From T3DB

Taxonomic Classification

Kingdom	Organic compounds
Superclass	Benzenoids
Class	Phenols
Subclass	Halophenols
Intermediate Tree Nodes	Chlorophenols
Direct Parent	P-chlorophenols
Alternative Parents	O-chlorophenols Hydrocarbon derivatives Aryl chlorides 1-hydroxy-2-unsubstituted benzenoids Organooxygen compounds M-chlorophenols Chlorobenzenes Organochlorides
Molecular Framework	Aromatic homomonocyclic compounds
Substituents	4-chlorophenol - 2-chlorophenol - 3-chlorophenol - 1-hydroxy-2-unsubstituted benzenoid - Halobenzene - Chlorobenzene - Monocyclic benzene moiety - Aryl halide - Aryl chloride - Organic oxygen compound - Hydrocarbon derivative - Organooxygen compound - Organochloride - Organohalogen compound - Aromatic homomonocyclic compound
Description	This compound belongs to the class of organic compounds known as p-chlorophenols. These are chlorophenols carrying a iodine at the C4 position of the benzene ring.

From ClassyFire

Targets

Target Details

ATP synthase subunit alpha, mitochondrial

General Function:: Transmembrane transporter activity
Specific Function:: Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F(1). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits. Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (By similarity).
Gene Name:: ATP5A1
Uniprot ID:: P25705
Molecular Weight:: 59750.06 Da

References

Janik F, Wolf HU: The Ca(2+)-transport-ATPase of human erythrocytes as an in vitro toxicity test system--acute effects of some chlorinated compounds. J Appl Toxicol. 1992 Oct;12(5):351-8. [1447481 ]

Target Details

Transient receptor potential cation channel subfamily A member 1

General Function:: Temperature-gated cation channel activity
Specific Function:: Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
Gene Name:: TRPA1
Uniprot ID:: O75762
Molecular Weight:: 127499.88 Da

References

Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]

From T3DB