Peringatan Keamanan

In general, the human ingestion of cresols results in burning of the mouth and throat, abdominal pain, and vomiting L992. The blood circulation, kidneys, lungs, liver, heart, and even the central nervous system have been reported as target sites for ingested cresols L992. Dermal exposure to cresols have been observed to cause severe skin burns, scarring, systemic toxicity, and even death L992. Acute exposures can result in severe burns, anuria, coma, and even possibly death L992. 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 L992.

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 L2015.

Moreover, one study suggests the lethal concentration of cresol in blood to be approximately 12 mg% (120 ug/mL) L992 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 L992.

Certain studies report the human lethal dose (LD) to be about 50-500 mg/kg bw L2019.

Cresol

DB11143

small molecule approved

Deskripsi

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.

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) There does not appear to be detailed information on the half-life of cresol in the human body [L2020]; 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 [L992] and laboratory animal [A32370] half-life values for administered cresol have been reported.
Volume Distribusi One study determined the volume of distribution of p-cresol in healthy rats as being approximately 2.9 +/- 1.4 L/kg [A32380]. 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 [L2038]. Otherwise, very little data about the distribution of cresols in the human body is available [L2038].
Klirens (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 [A32376]. 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 [A32376]. 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 [A32376]. Additionally, endogenous p-cresol is produced from tyrosine, an amino acid that is found in most proteins, by anaerobic bacteria in the intestine [L2038]. 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 [L2038].

Absorpsi

In general, it is believed that cresols can be absorbed through intact skin and across respiratory and gastrointestinal linings L2038. 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 A32381. 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 A32381. 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 A32381.

Metabolisme

Once absorbed, cresols are mainly metabolized by the liver L992 and result in metabolites that are conjugated with glucuronic acid and inorganic sulfate and excreted as conjugates in the urine L2019. Some primary metabolites that have been documented subsequently include p-cresyl sulfate and the glucuronide p-cresol metabolite L992.

Rute Eliminasi

The major route of excretion is likely in the urine L992.

Interaksi Obat

1 Data
Tenofovir alafenamide The serum concentration of Tenofovir alafenamide can be increased when it is combined with Cresol.

Referensi & Sumber

Artikel (PubMed)
  • PMID: 12969155
    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.
  • PMID: 27084876
    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.
  • PMID: 20067224
    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.
  • PMID: 11669466
    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.
  • PMID: 22602
    Roberts MS, Anderson RA, Swarbrick J: Permeability of human epidermis to phenolic compounds. J Pharm Pharmacol. 1977 Nov;29(11):677-83.
  • PMID: 14452711
    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.

Contoh Produk & Brand

Produk: 4 • International brands: 0
Produk
  • Buckleys Formo Cresol
    Liquid • 350 mg/1g • Dental • US
  • Formo Cresol
    Liquid • 485 mg/1g • Dental • US
  • Formo Cresol
    Liquid • 485 mg/1g • Dental • US
  • Root Canal Therapy
    Liquid • - • Dental • Canada • OTC • Approved

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