Identification
- Summary
Cresol is a dental disinfectant used to remove dental pulp.
- Generic Name
- Cresol
- DrugBank Accession Number
- DB11143
- Background
Cresol is a hydroxytoluene that can be extracted naturally from coal tar or made synthetically. Pure cresol is a mixture of ortho-, meta-, and para- isomers. Cresols are precursors or synthetic intermediates to various other compounds and materials, including plastics, pesticides, pharmaceuticals, disinfectants, and dyes. Ingestion of cresol induces toxicity in humans and can lead to burning of the mouth and throat, abdominal pain, and/or vomiting. At concentrations normally found in the environment however, cresols do not pose any significant risk for the general population.
- Type
- Small Molecule
- Groups
- Approved
- Synonyms
- Cresol
Pharmacology
- Indication
The primary medical indications for cresols in general include being used as bactericides, pesticides, and disinfectants 10. Certain isomers of cresol, like m-cresol, may be used as inactive ingredients for the purpose of serving as a preservative in some pharmaceuticals 10.
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All cresol isomers are absorbed across the respiratory and gastrointestinal tract and through the intact skin 9. Limited data indicate that cresols are widely distributed throughout the body after uptake 9. Cresols are mainly conjugated with glucuronic acid and inorganic sulfate and excreted as conjugates with the urine 9.
At physiological pH, the conjugated metabolites are ionized to a greater extent than the parent compound, which reduces renal reabsorption and increases elimination with the urine 9. In addition to urinary excretion, cresols are excreted in the bile, but the most part undergoes enterohepatic circulation 9. There are know species differences in the specific conjugation reactions of cresol isomers and the relative amounts of glucuronide and sulfate conjugates therefore differ between species and also vary with dose 9.
- Mechanism of action
When cresol isomers are used directly as the active ingredient in bactericides or disinfectants, it appears as if much of the evidence for the mechanism of action for such phenolic germicides indicates that their effect is due to physical damage of bacterial cell membranes 6. Although not completely explained, some possibilities of how this effect occurs either involves the phenol germicide binding or coming into contact with and (a) causing changes in the permeability of the osmotic barrier of bacterial cell membranes, which therefore allows the escape or leakage of normal cytoplasmic constituents, (b) causing the uncoupling of cytoplasmic constituents with their subsequent leakage from the cell, or (c) a combination of these actions 6.
- Absorption
In general, it is believed that cresols can be absorbed through intact skin and across respiratory and gastrointestinal linings 11. Although the rates and extents to which cresols are absorbed across the lungs and gastrointestinal tract do not yet appear to have been studied in detail, an in-vitro study regarding the permeability of human skin to cresols demonstrated that cresols possess permeability coefficients larger than that of phenol, which is already known to be readily absorbed across the human skin 5. In particular, the permeability coefficients (Kp) were approximated from the steady-state slopes of the relation between the cumulative amount of cresol isomer per unit area of membrane with time 5. The particular Kp values calculated for m-, o-, and p-cresol were 2.54 x 10^-4, 2.6 x 10^-4, and 2.92 x 10^-4 cm/minute, respectively 5.
- Volume of distribution
One study determined the volume of distribution of p-cresol in healthy rats as being approximately 2.9 +/- 1.4 L/kg 4.
Nevertheless, one case study reports detecting cresols in the blood (120 mg/litre), liver, brain, and urine of a human infant who passed away four hours after 20 ml of a cresol derivative had spilled on the infant's head 11. Otherwise, very little data about the distribution of cresols in the human body is available 11.
- Protein binding
P-cresyl sulfate and p-cresol, both of which are primary cresol metabolites that have been documented, have been observed to demonstrate relatively low protein binding with human serum albumin at about 13-20% binding 3. The affinity of p-cresyl sulfate and p-cresol toward human serum albumin is evidently moderate at 25 degrees Celsius and becomes relatively weak at physiological temperature, 37 degrees Celsius 3. Such protein binding largely involves van Der Waals category of interactions, and the binding sites of the two moieties are either identical or extremely close in proximity 3.
- Metabolism
Once absorbed, cresols are mainly metabolized by the liver 7 and result in metabolites that are conjugated with glucuronic acid and inorganic sulfate and excreted as conjugates in the urine 9. Some primary metabolites that have been documented subsequently include p-cresyl sulfate and the glucuronide p-cresol metabolite 7.
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- Route of elimination
The major route of excretion is likely in the urine 7.
- Half-life
There does not appear to be detailed information on the half-life of cresol in the human body 10; the pharmacokinetics of cresol in the human body is usually discussed in the context of accidental exposure and ingestion and not as a formal research study. Nevertheless, various environmental 7 and laboratory animal 1 half-life values for administered cresol have been reported.
- Clearance
As colonic microbial metabolism contributes significantly to uremic retention solutes in patients with chronic kidney disease, one study estimated the clearance of p-Cresyl sulfate and the glucuronide p-cresol metabolite - both of which are metabolites of cresol and representative uremic retention solutes - in such patients.
The total renal clearance of p-Cresyl sulfate was median 6.6 ml/min while that of the glucuronide p-cresol metabolite was median 98.9 ml/min 2. Furthermore, the free solute renal clearance of p-Cresyl sulfate and the glucuronide p-cresol metabolite were observed to be about median 190,0 ml/min and about median 136.5 ml/min, respectively 2. These results were obtained for a specific subject population that was comprised of 488 patients with chronic kidney disease stages 1 through 5, demonstrating a mean eGFR (ml/min per 1.73 m2) of 35 2.
Additionally, endogenous p-cresol is produced from tyrosine, an amino acid that is found in most proteins, by anaerobic bacteria in the intestine 11. It has been observed that healthy humans generally excrete an average of approximately 50 mg (out of a range of 16 to 74 mg) of such endogenously generated p-cresol daily in the urine 11.
- Adverse Effects
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In general, the human ingestion of cresols results in burning of the mouth and throat, abdominal pain, and vomiting 7. The blood circulation, kidneys, lungs, liver, heart, and even the central nervous system have been reported as target sites for ingested cresols 7. Dermal exposure to cresols have been observed to cause severe skin burns, scarring, systemic toxicity, and even death 7. Acute exposures can result in severe burns, anuria, coma, and even possibly death 7. Cresol, in its general form is very unlikely to be indicated or used as any kind of health product for humans or animals to ingest or apply 7.
The Immediately Dangerous to Life or Health (IDLH) value as documented by the Centers for Disease Control and Prevention (CDC) National Institute for Occupational Safety and Health (NIOSH) for cresol (comprised of the ortho-, meta-, and para- isomers) is 250 ppm, based upon acute inhalation toxicity data in animals 8.
Moreover, one study suggests the lethal concentration of cresol in blood to be approximately 12 mg% (120 ug/mL) 7 and the smallest amount of cresol that produced death was 4 mL of a 25% to 50% cresol solution in an 11 month old child 7.
Certain studies report the human lethal dose (LD) to be about 50-500 mg/kg bw 9.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareTenofovir alafenamide The serum concentration of Tenofovir alafenamide can be increased when it is combined with Cresol. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Active Moieties
Name Kind UNII CAS InChI Key Formaldehyde unknown 1HG84L3525 50-00-0 WSFSSNUMVMOOMR-UHFFFAOYSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Buckleys Formo Cresol Liquid 350 mg/1g Dental Dentsply LLC, Professional Division Trading as "Sultan Healthcare" 1963-02-19 Not applicable US 
Formo Cresol Liquid 485 mg/1g Dental Ds Healthcare 1963-02-19 Not applicable US Formo Cresol Liquid 485 mg/1g Dental Ds Healthcare 1963-02-19 Not applicable US - Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image ครีโซล Solution 100 ml/100ml ห้างหุ้นส่วนจำกัด โรงงานผลิตยาอันอันโอสถ 1988-01-20 Not applicable Thailand 
ไลโซล Solution 50 ml/100ml บริษัท วิทยาศรม จำกัด 1986-11-07 Not applicable Thailand - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Root Canal Therapy Cresol (35 %) + Formaldehyde (19 %) Liquid Dental Amd Medicom Inc 1999-11-26 2006-08-03 Canada 
- Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Buckleys Formo Cresol Cresol (350 mg/1g) Liquid Dental Dentsply LLC, Professional Division Trading as "Sultan Healthcare" 1963-02-19 Not applicable US Formo Cresol Cresol (485 mg/1g) Liquid Dental Ds Healthcare 1963-02-19 Not applicable US Formo Cresol Cresol (485 mg/1g) Liquid Dental Ds Healthcare 1963-02-19 Not applicable US
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- GF3CGH8D7Z
- CAS number
- 1319-77-3
- InChI Key
- Not Available
- InChI
- Not Available
- IUPAC Name
- Not Available
- SMILES
- Not Available
References
- General References
- Lesaffer G, De Smet R, D'Heuvaert T, Belpaire FM, Lameire N, Vanholder R: Comparative kinetics of the uremic toxin p-cresol versus creatinine in rats with and without renal failure. Kidney Int. 2003 Oct;64(4):1365-73. doi: 10.1046/j.1523-1755.2003.00228.x. [Article]
- Poesen R, Evenepoel P, de Loor H, Kuypers D, Augustijns P, Meijers B: Metabolism, Protein Binding, and Renal Clearance of Microbiota-Derived p-Cresol in Patients with CKD. Clin J Am Soc Nephrol. 2016 Jul 7;11(7):1136-44. doi: 10.2215/CJN.00160116. Epub 2016 Apr 15. [Article]
- Berge-Lefranc D, Chaspoul F, Calaf R, Charpiot P, Brunet P, Gallice P: Binding of p-cresylsulfate and p-cresol to human serum albumin studied by microcalorimetry. J Phys Chem B. 2010 Feb 4;114(4):1661-5. doi: 10.1021/jp9059517. [Article]
- Lesaffer G, De Smet R, D'heuvaert T, Belpairea FM, Lameire N, Vanholder R: Kinetics of the protein-bound, lipophilic, uremic toxin p-cresol in healthy rats. Life Sci. 2001 Sep 28;69(19):2237-48. [Article]
- Roberts MS, Anderson RA, Swarbrick J: Permeability of human epidermis to phenolic compounds. J Pharm Pharmacol. 1977 Nov;29(11):677-83. [Article]
- JUDIS J: Studies on the mechanism of action of phenolic disinfectants. I. Release of radioactivity from carbon-14-labeled Escherichia coli. J Pharm Sci. 1962 Mar;51:261-5. [Article]
- TOXNET: Cresol [Link]
- CDC NIOSH: Cresol (o, m, p isomers) [Link]
- OCED SIDS UNEP Publications: M/P-Cresol Catgory [Link]
- Interim Specific Ground Water Criterion: o, m, p-Cresol [Link]
- International Programme On Chemical Safety (IPCS) INCHEM Environmental Health Criteria 168: Cresols [Link]
- IPCS INCHEM: o-cresol [Link]
- IPCS INCHEM: m-cresol [Link]
- IPCS INCHEM: p-cresol [Link]
- External Links
- MSDS
- Download (123 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count Not Available Unknown Status Treatment Dental Decay / Pulpitis dental 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Liquid Dental 350 mg/1g Liquid Dental 485 mg/1g Liquid Dental Solution 100 ml/100ml Solution 50 ml/100ml - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) o-cresol: 29.8/ m-cresol: 11.8/ p-cresol: 35.5 Not Available boiling point (°C) o-cresol: 191.0/ m-cresol: 202.0/ p-cresol: 201.9 Not Available water solubility o-cresol: 2.5g/100ml / m-cresol: 2.4g/100ml / p-cresol: 1.9g/100ml Not Available pKa o-cresol: 10.287/ m-cresol: 10.09/ p-cresol: 10.26 Not Available - Predicted Properties
- Not Available
- Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Drug created at December 03, 2015 16:51 / Updated at February 21, 2021 18:52