You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version4.0
Creation Date2006-02-22 10:50:16 UTC
Update Date2017-09-27 08:24:09 UTC
HMDB IDHMDB0001858
Secondary Accession Numbers
  • HMDB01858
  • HMDB13762
Metabolite Identification
Common Namep-Cresol
Descriptionp-Cresol (4-methylphenol), a 108.1 Da volatile low-molecular-weight compound, is a phenol. It is a partially lipophilic moiety which strongly binds to plasma protein (close to 100%) under normal conditions. p-Cresol is metabolized through conjugation, mainly sulphation and glucuronization, but removal of the unconjugated p-cresol is, at least in part, via the urine. Therefore it is not surprising that this compound, together with several other phenoles, is retained when the kidneys fail. P-Cresol is an end-product of protein breakdown, and an increase of the nutritional protein load in healthy individuals results in enhanced generation and urinary excretion. The serum p-cresol concentration in uremic patients can be decreased by changing to a low-protein diet. p-Cresol is one of the metabolites of the amino acid tyrosine, and to a certain extent also of phenylalanine, which are converted to 4-hydroxyphenylacetic acid by intestinal bacteria, before being decarboxylated to p-cresol (putrefaction). The main contributing bacteria are aerobes (mainly enterobacteria), but to a certain extent also anaerobes play a role (mainly Clostridium perfringens). In uremia, modifications in the intestinal flora result in the specific overgrowth of bacteria that are specific p-cresol producers. The administration of antibiotics reduces urinary excretion of p-cresol, as a result of the liquidation of the producing bacteria. Environmental factors might also contribute. The liver cytochrome P450 metabolizes toluene to benzyl alcohol, but also to o-cresol and p-cresol. Toluene is not only used industrially, but it is also the most widely abusively inhaled solvent. Furthermore, p-cresol is a metabolite of menthofuran, one of the metabolites of R-(+)-pulegone, which is found in extracts from the plants Mentha pulegium and Hedeoma pulegioides, commonly known as pennyroyal oil and pennyroyal tea. These extracts are popular as unconventional herbal therapeutic agents and are applied as abortiva, diaphoretics, emmenagogues, and psychedelic drugs. Pennyroyal oil is extensively used for its pleasant mint-like smell in the flavoring industry. The toxicity of pennyroyal oil and menthofuran is well known. Another compound used in traditional medicine, especially in Japan, which is a precursor of p-cresol is wood tar creosote. p-Cresol has been reported to affect several biochemical, biological and physiological functions: (i) it diminishes the oxygen uptake of rat cerebral cortex slices; (ii) it increases the free active drug concentration of warfarin and diazepam; (iii) it has been related to growth retardation in the weanling pig; (iv) it alters cell membrane permeability, at least in bacteria; (v) it induces LDH leakage from rat liver slices; (vi) it induces susceptibility to auditive epileptic crises; and (vii) it blocks cell K+ channels. (PMID: 10570076 ). p-Cresol is a uremic toxin that is at least partially removed by peritoneal dialysis in haemodialysis patients, and has been involved in the progression of renal failure. (MID: 11169029). At concentrations encountered during uremia, p-cresol inhibits phagocyte function and decreases leukocyte adhesion to cytokine-stimulated endothelial cells. (PMID: 14681860 ).
Structure
Thumb
Synonyms
ValueSource
1-Hydroxy-4-methylbenzeneChEBI
4-CresolChEBI
4-HydroxytolueneChEBI
4-MethylphenolChEBI
P-KresolChEBI
P-MethylphenolChEBI
P-Tolyl alcoholChEBI
ParacresolChEBI
1-Methyl-4-hydroxybenzeneHMDB
4-(Pentafluorosulfanyl)phenolHMDB
4-Methyl phenolHMDB
4-Methyl-phenolHMDB
P-CresylateHMDB
P-Cresylic acidHMDB
P-HydroxytolueneHMDB
P-Methyl phenolHMDB
P-MethylhydroxybenzeneHMDB
P-OxytolueneHMDB
P-ToluolHMDB
Paramethyl phenolHMDB
4-Cresol, potassium saltMeSH
m-CresolMeSH
4-Cresol, aluminum saltMeSH
4-Cresol, sodium saltMeSH
Para-cresolMeSH
Chemical FormulaC7H8O
Average Molecular Weight108.1378
Monoisotopic Molecular Weight108.057514878
IUPAC Name4-methylphenol
Traditional NameP-cresol
CAS Registry Number106-44-5
SMILES
CC1=CC=C(O)C=C1
InChI Identifier
InChI=1S/C7H8O/c1-6-2-4-7(8)5-3-6/h2-5,8H,1H3
InChI KeyIWDCLRJOBJJRNH-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities 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.
KingdomChemical entities
Super ClassOrganic compounds
ClassBenzenoids
Sub ClassPhenols
Direct ParentPara cresols
Alternative Parents
Substituents
  • P-cresol
  • 1-hydroxy-2-unsubstituted benzenoid
  • Toluene
  • Monocyclic benzene moiety
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

  Tissue and substructures:

  Cell and elements:

    Cell:

Source:

Route of exposure:

  Parenteral:

  Enteral:

Role

Industrial application:

  Pharmaceutical industry:

Indirect biological role:

Physiological effect

Health effect:

  Health condition:

    Psychiatric disorders:

    Gastrointestinal disorders:

    Nervous system disorders:

    General disorders and administration site conditions:

    Musculoskeletal and connective tissue disorders:

    Metabolism and nutrition disorders:

    Vascular disorders:

  Observation:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point35.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility21.5 mg/mL at 25 °CNot Available
LogP1.94HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility23.1 g/LALOGPS
logP1.95ALOGPS
logP2.18ChemAxon
logS-0.67ALOGPS
pKa (Strongest Acidic)10.36ChemAxon
pKa (Strongest Basic)-5.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity33.08 m³·mol⁻¹ChemAxon
Polarizability11.93 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a4i-5900000000-1d2bdfde621a5af9be73View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a4i-5900000000-b76093f53701327ab25fView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a4i-4900000000-7d25deb1e39c6ef4866fView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a4i-7900000000-15d473146e11e4b049b2View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-014l-4900000000-14fef90a661a09457976View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-6900000000-27534de20ade11dd5454View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-06fr-9700000000-f41dd95ca553de6bafffView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0a4i-5900000000-ab55ada5cae0538f383eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0006-9000000000-385a7a99e0409c7f060dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-02tl-9000000000-205f4e5245868e9debccView in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (VARIAN MAT-44) , Positivesplash10-0a4i-5900000000-fd438231ac0ed75fdf09View in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI RMU-7M) , Positivesplash10-0a4i-5900000000-b76093f53701327ab25fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (JEOL JMS-D-3000) , Positivesplash10-0a4i-4900000000-7d25deb1e39c6ef4866fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-80B) , Positivesplash10-0a4i-7900000000-0cdab17a1a95f3e65f45View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0900000000-cf0bed2b3a203309d9aaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-1900000000-4f20c8bd2dde845b499cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0fb9-9100000000-393b5f734646352622f9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0900000000-0c45920f40546c2d8944View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0900000000-417774c01b748db1609dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9600000000-5583b6dc3ae583b8dab0View in MoNA
MSMass Spectrum (Electron Ionization)splash10-0a4i-6900000000-729e6f5bdb0da3ed9dedView in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
  • Feces
  • Saliva
  • Urine
Tissue Location
  • Adipose Tissue
  • Fibroblasts
PathwaysNot Available
NameSMPDB/PathwhizKEGG
No entries found
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot Available
Normal
    details
    FecesDetected but not Quantified Not SpecifiedNot Specified
    Normal
    details
    FecesDetected but not Quantified Not SpecifiedNot Specified
    Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)BothNormal details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    FecesDetected and Quantified233.74 - 993.94 ppmChildren (1-13 years old)Not Specified
    Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)BothNormal details
    FecesDetected but not Quantified Adult (>18 years old)BothNormal details
    FecesDetected but not Quantified Children (1-13 years old)BothNormal details
    FecesDetected but not Quantified Not SpecifiedNot Specified
    Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    FecesDetected and Quantified136.585 +/- 69.263 uMNot SpecifiedNot Specified
    Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)BothNormal details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    FecesDetected and Quantified95.249 +/- 98.948 uMNot SpecifiedNot Specified
    Normal
    details
    FecesDetected but not Quantified Children (1-13 years old)Not Specified
    Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    FecesDetected but not Quantified Newborn (0-30 days old)Both
    Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    SalivaDetected but not Quantified Adult (>18 years old)Not SpecifiedNormal details
    UrineDetected and Quantified17.6 (17.6-17.6) umol/mmol creatinineNewborn (0-30 days old)BothNormal details
    UrineDetected and Quantified24.7 (1.2-110.7) umol/mmol creatinineChildren (1-13 years old)Both
    Normal
    details
    UrineDetected and Quantified46.0 (1.2-118.9) umol/mmol creatinineAdult (>18 years old)Both
    Normal
    details
    UrineDetected and Quantified23.0 (11.4-114.0) umol/mmol creatinineAdolescent (13-18 years old)Both
    Normal
    details
    UrineDetected and Quantified0.13 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    UrineDetected and Quantified52.6 (38.8-71.0) umol/mmol creatinineAdult (>18 years old)BothNormal
      • Geigy Scientific ...
    details
    UrineDetected and Quantified2.933 +/- 2.099 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
    Normal
      • Mordechai, Hien, ...
    details
    UrineDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    Abnormal Concentrations
    BiofluidStatusValueAgeSexConditionReferenceDetails
    BloodDetected and Quantified9.9 +/- 5.1 uMAdult (>18 years old)BothHemodialysis details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Campylobacter jejuni infection
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Clostridium difficile infection
    details
    FecesDetected and Quantified0 - 977.15 ppmChildren (1-13 years old)Not Specified
    Treated celiac disease
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Ulcerative Colitis
    details
    FecesDetected but not Quantified Adult (>18 years old)BothImmunoglobulin A nephropathy (IgAN) non progressor details
    FecesDetected but not Quantified Adult (>18 years old)BothImmunoglobulin A nephropathy (IgAN) progressor details
    FecesDetected but not Quantified Children (1-13 years old)BothAutism details
    FecesDetected but not Quantified Children (1-13 years old)BothPervasive Developmental Disorder Not Otherwise Specified details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Irritable bowel syndrome
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Ulcerative colitis
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Ulcerative colitis
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Crohn's disease
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Nonalcoholic fatty liver disease (NAFLD)
    details
    FecesDetected but not Quantified Children (1-13 years old)Not Specified
    Treated celiac disease
    details
    FecesDetected but not Quantified Adult (>18 years old)BothColorectal Cancer details
    FecesDetected but not Quantified Not SpecifiedNot Specified
    Crohn's disease
    details
    FecesDetected but not Quantified Not SpecifiedNot Specified
    Ulcerative colitis
    details
    FecesDetected and Quantified0.00197 (0.000166-0.00543) uMNot SpecifiedNot Specified
    Irritable bowel syndrome
    details
    FecesDetected and Quantified0.00204 (0.00108-0.00888) uMNot SpecifiedNot Specified
    Ulcerative colitis
    details
    FecesDetected and Quantified0.00461 (0.00106-0.0113) uMNot SpecifiedNot Specified
    Crohns disease
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Diarrhea-predominant IBS
    details
    UrineDetected and Quantified5.14 +/- 2.998 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
    Eosinophilic esophagitis
      • Mordechai, Hien, ...
    details
    UrineDetected but not Quantified Adult (>18 years old)Both
    Colorectal cancer
    details
    UrineDetected but not Quantified Adult (>18 years old)BothColorectal cancer details
    Associated Disorders and Diseases
    Disease References
    Hemodialysis
    1. De Smet R, Van Kaer J, Liebich H, Lesaffer G, Verstraete A, Dhondt A, Duym P, Lameire N, Vanholder R: Heparin-induced release of protein-bound solutes during hemodialysis is an in vitro artifact. Clin Chem. 2001 May;47(5):901-9. [PubMed:11325895 ]
    Associated OMIM IDsNone
    DrugBank IDDB01688
    DrugBank Metabolite IDNot Available
    Phenol Explorer Compound IDNot Available
    Phenol Explorer Metabolite IDNot Available
    FoodDB IDFDB008789
    KNApSAcK IDC00002645
    Chemspider ID13839082
    KEGG Compound IDC01468
    BioCyc IDCPD-108
    BiGG IDNot Available
    Wikipedia Linkp-Cresol
    METLIN ID4236
    PubChem Compound2879
    PDB IDPCR
    ChEBI ID17847
    References
    Synthesis ReferenceNot Available
    Material Safety Data Sheet (MSDS)Download (PDF)
    General References
    1. Geyer H, Scheunert I, Korte F: Bioconcentration potential of organic environmental chemicals in humans. Regul Toxicol Pharmacol. 1986 Dec;6(4):313-47. [PubMed:3101145 ]
    2. 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. [PubMed:11476216 ]
    3. 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. [PubMed:11334365 ]
    4. 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. [PubMed:8887339 ]
    5. 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. [PubMed:826152 ]
    6. 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. [PubMed:8408385 ]
    7. 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. [PubMed:16441915 ]
    8. 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. [PubMed:2121515 ]
    9. 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. [PubMed:11440127 ]
    10. 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. [PubMed:9448067 ]
    11. 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. [PubMed:14633143 ]
    12. Brunet P, Dou L, Cerini C, Berland Y: Protein-bound uremic retention solutes. Adv Ren Replace Ther. 2003 Oct;10(4):310-20. [PubMed:14681860 ]
    13. 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. [PubMed:10570076 ]