4-Methylphenol

Relevant Data

Food Additives Approved in the United States:

Food Additives Approved by WHO:

General Information

Chemical name4-Methylphenol
CAS number106-44-5
COE number619
JECFA number693
Flavouring typesubstances
FL No.04.028
MixtureNo
Purity of the named substance at least 95% unless otherwise specified

From webgate.ec.europa.eu

Computed Descriptors

Download SDF
2D Structure
CID2879
IUPAC Name4-methylphenol
InChIInChI=1S/C7H8O/c1-6-2-4-7(8)5-3-6/h2-5,8H,1H3
InChI KeyIWDCLRJOBJJRNH-UHFFFAOYSA-N
Canonical SMILESCC1=CC=C(C=C1)O
Molecular FormulaC7H8O
Wikipediapara-cresol

From Pubchem

Computed Properties

Property Name Property Value
Molecular Weight108.14
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count1
Rotatable Bond Count0
Complexity62.8
CACTVS Substructure Key Fingerprint A A A D c c B g I A A A 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 A A C A A A D A S A m A A y B o A A A g C A A i B C A A A C A A A g I A A I i A A G C I g I J i K C E R K A c A A k w B E I m A e A w A A O I A A A A A A A A A B A A A A A A A A A A A A A A A A A A A = =
Topological Polar Surface Area20.2
Monoisotopic Mass108.058
Exact Mass108.058
Compound Is CanonicalizedTrue
Formal Charge0
Heavy Atom Count8
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

From Pubchem

Food Additives Biosynthesis/Degradation

ADMET Predicted Profile --- Classification

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.8911
Human Intestinal AbsorptionHIA+0.9960
Caco-2 PermeabilityCaco2+0.9256
P-glycoprotein SubstrateNon-substrate0.7504
P-glycoprotein InhibitorNon-inhibitor0.9753
Non-inhibitor0.9910
Renal Organic Cation TransporterNon-inhibitor0.8770
Distribution
Subcellular localizationMitochondria0.7469
Metabolism
CYP450 2C9 SubstrateNon-substrate0.7251
CYP450 2D6 SubstrateNon-substrate0.8554
CYP450 3A4 SubstrateNon-substrate0.7152
CYP450 1A2 InhibitorInhibitor0.5105
CYP450 2C9 InhibitorNon-inhibitor0.9606
CYP450 2D6 InhibitorNon-inhibitor0.9789
CYP450 2C19 InhibitorNon-inhibitor0.9343
CYP450 3A4 InhibitorNon-inhibitor0.9324
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.8870
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.8281
Non-inhibitor0.9609
AMES ToxicityNon AMES toxic0.9513
CarcinogensNon-carcinogens0.7350
Fish ToxicityHigh FHMT0.6839
Tetrahymena Pyriformis ToxicityHigh TPT0.9286
Honey Bee ToxicityHigh HBT0.8261
BiodegradationReady biodegradable0.6121
Acute Oral ToxicityII0.7716
Carcinogenicity (Three-class)Non-required0.6111

From admetSAR

ADMET Predicted Profile --- Regression

Model Value Unit
Absorption
Aqueous solubility-0.6374LogS
Caco-2 Permeability1.6148LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.5863LD50, mol/kg
Fish Toxicity1.3626pLC50, mg/L
Tetrahymena Pyriformis Toxicity-0.2094pIGC50, ug/L

From admetSAR

Toxicity Profile

Route of ExposureInhalation ; dermal ; oral
Mechanism of Toxicityp-Cresol is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
MetabolismCresols can be absorbed following inhalation, oral, and dermal exposure. Once in the body they can distribute rapidly into many organs and tissues. Cresols undergo oxidative metabolism in the liver and are rapidly eliminated, mostly in the urine, as sulfate or glucuronide conjugates. The activation of cresols by oxidation involves tyrosinase and thyroid peroxidase, forming a reactive quinone methide. Experiments with recombinant P-450s demonstrated cresol metabolism was mediated by several P-450s including CYP2D6, 2C19, 1A2, 1A1, and 2E1.
Toxicity ValuesLD50: 207 mg/kg (Oral, Rat) LD50: 301 mg/kg (Dermal, Rabbit) LD50: 25 mg/kg (Intraperitoneal, Mouse)
Lethal DoseNone
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Minimum Risk LevelIntermediate Oral: 0.1 mg/kg/day Chronic Oral: 0.1 mg/kg/day
Health EffectsAcute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
TreatmentIf the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
Reference
  1. Yan Z, Zhong HM, Maher N, Torres R, Leo GC, Caldwell GW, Huebert N: Bioactivation of 4-methylphenol (p-cresol) via cytochrome P450-mediated aromatic oxidation in human liver microsomes. Drug Metab Dispos. 2005 Dec;33(12):1867-76. Epub 2005 Sep 20.[16174805 ]
  2. Yokoi H, Belfort G: High-rate membrane supported aqueous-phase enzymatic conversion in organic solvent. Bioseparation. 1994 Jun;4(3):213-20.[7765181 ]
  3. Brunet P, Dou L, Cerini C, Berland Y: Protein-bound uremic retention solutes. Adv Ren Replace Ther. 2003 Oct;10(4):310-20.[14681860 ]
  4. Ogata N, Shibata T: Binding of alkyl- and alkoxy-substituted simple phenolic compounds to human serum proteins. Res Commun Mol Pathol Pharmacol. 2000;107(1-2):167-73.[11334365 ]
  5. Vanholder R, De Smet R, Lesaffer G: p-cresol: a toxin revealing many neglected but relevant aspects of uraemic toxicity. Nephrol Dial Transplant. 1999 Dec;14(12):2813-5.[10570076 ]
  6. Cork A, Park KC: Identification of electrophysiologically-active compounds for the malaria mosquito, Anopheles gambiae, in human sweat extracts. Med Vet Entomol. 1996 Jul;10(3):269-76.[8887339 ]
  7. Bone E, Tamm A, Hill M: The production of urinary phenols by gut bacteria and their possible role in the causation of large bowel cancer. Am J Clin Nutr. 1976 Dec;29(12):1448-54.[826152 ]
  8. Buhlmann P, Hayakawa M, Ohshiro T, Amemiya S, Umezawa Y: Influence of natural, electrically neutral lipids on the potentiometric responses of cation-selective polymeric membrane electrodes. Anal Chem. 2001 Jul 15;73(14):3199-205.[11476216 ]
  9. Akasaka K, Ohrui H, Meguro H, Tamura M: Determination of triacylglycerol and cholesterol ester hydroperoxides in human plasma by high-performance liquid chromatography with fluorometric postcolumn detection. J Chromatogr. 1993 Aug 11;617(2):205-11.[8408385 ]
  10. Gostner A, Blaut M, Schaffer V, Kozianowski G, Theis S, Klingeberg M, Dombrowski Y, Martin D, Ehrhardt S, Taras D, Schwiertz A, Kleessen B, Luhrs H, Schauber J, Dorbath D, Menzel T, Scheppach W: Effect of isomalt consumption on faecal microflora and colonic metabolism in healthy volunteers. Br J Nutr. 2006 Jan;95(1):40-50.[16441915 ]
  11. Letelier ME, Rodriguez E, Wallace A, Lorca M, Repetto Y, Morello A, Aldunate J: Trypanosoma cruzi: a possible control of transfusion-induced Chagas' disease by phenolic antioxidants. Exp Parasitol. 1990 Nov;71(4):357-63.[2121515 ]
  12. Geyer H, Scheunert I, Korte F: Bioconcentration potential of organic environmental chemicals in humans. Regul Toxicol Pharmacol. 1986 Dec;6(4):313-47.[3101145 ]
  13. Nishiyama T, Ohnishi J, Hashiguchi Y: Fused heterocyclic antioxidants: antioxidative activities of hydrocoumarins in a homogeneous solution. Biosci Biotechnol Biochem. 2001 May;65(5):1127-33.[11440127 ]
  14. Dills RL, Bellamy GM, Kalman DA: Quantitation of o-, m- and p-cresol and deuterated analogs in human urine by gas chromatography with electron capture detection. J Chromatogr B Biomed Sci Appl. 1997 Dec 5;703(1-2):105-13.[9448067 ]
  15. Bammens B, Verbeke K, Vanrenterghem Y, Evenepoel P: Evidence for impaired assimilation of protein in chronic renal failure. Kidney Int. 2003 Dec;64(6):2196-203.[14633143 ]

From T3DB

Taxonomic Classification

KingdomOrganic compounds
SuperclassBenzenoids
ClassPhenols
SubclassCresols
Intermediate Tree NodesNot available
Direct ParentPara cresols
Alternative Parents
Molecular FrameworkAromatic homomonocyclic compounds
SubstituentsP-cresol - 1-hydroxy-2-unsubstituted benzenoid - Toluene - Monocyclic benzene moiety - Organic oxygen compound - Hydrocarbon derivative - Organooxygen compound - Aromatic homomonocyclic compound
DescriptionThis compound belongs to the class of organic compounds known as para cresols. These are compounds containing a para cresol moiety, which consists of a benzene ring bearing one hydroxyl group at ring positions 1 and 4.

From ClassyFire

Targets

Target Details

Lactoperoxidase

General Function:
Thiocyanate peroxidase activity
Specific Function:
Antimicrobial agent which utilizes hydrogen peroxide and thiocyanate (SCN) to generate the antimicrobial substance hypothiocyanous acid (HOSCN) (By similarity). May contribute to airway host defense against infection.
Gene Name:
LPO
Uniprot ID:
P22079
Molecular Weight:
80287.055 Da
References
  1. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
Target Details

Acetylcholinesterase

General Function:
Serine hydrolase activity
Specific Function:
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name:
ACHE
Uniprot ID:
P22303
Molecular Weight:
67795.525 Da
References
  1. Cardozo MG, Iimura Y, Sugimoto H, Yamanishi Y, Hopfinger AJ: QSAR analyses of the substituted indanone and benzylpiperidine rings of a series of indanone-benzylpiperidine inhibitors of acetylcholinesterase. J Med Chem. 1992 Feb 7;35(3):584-9. [1738151 ]
Target Details

Dopamine beta-hydroxylase

General Function:
L-ascorbic acid binding
Specific Function:
Conversion of dopamine to noradrenaline.
Gene Name:
DBH
Uniprot ID:
P09172
Molecular Weight:
69064.45 Da
References
  1. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
Target Details

Fas-binding factor 1

Specific Function:
Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis.
Gene Name:
FBF1
Uniprot ID:
Q8TES7
Molecular Weight:
125445.19 Da
References
  1. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
Target Details

Myeloperoxidase

General Function:
Peroxidase activity
Specific Function:
Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity.
Gene Name:
MPO
Uniprot ID:
P05164
Molecular Weight:
83867.71 Da
References
  1. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
Target Details

Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase

General Function:
Nicotinate-nucleotide-dimethylbenzimidazole phosphoribosyltransferase activity
Specific Function:
Catalyzes the synthesis of alpha-ribazole-5'-phosphate from nicotinate mononucleotide (NAMN) and 5,6-dimethylbenzimidazole (DMB).
Gene Name:
cobT
Uniprot ID:
Q05603
Molecular Weight:
36612.305 Da

From T3DB