T3D1842

1846 T3D1842

m-Cresol

m-Cresol is an isomer of p-cresol and o-cresol. Cresols are organic compounds which are methylphenols. They are a widely occurring natural and manufactured group of aromatic organic compounds which are categorized as phenols (sometimes called phenolics). Depending on the temperature, cresols can be solid or liquid because they have melting points not far from room temperature. Like other types of phenols, they are slowly oxidized by long exposure to air and the impurities often give cresols a yellowish to brownish red tint. Cresols have an odor characteristic to that of other simple phenols, reminiscent to some of a medicine smell. Cresol solutions are used as household cleaners and disinfectants, perhaps most famously under the trade name Lysol. In the past, cresol solutions have been used as antiseptics in surgery, but they have been largely displaced in this role by less toxic compounds. Lysol was also advertised as a disinfecting vaginal douche in mid-twentieth century America. Cresols are found in many foods and in wood and tobacco smoke, crude oil, coal tar, and in brown mixtures such as creosote and cresylic acids, which are wood preservatives. Small organisms in soil and water produce cresols when they break down materials in the environment. Most exposures to cresols are at very low levels that are not harmful. When cresols are breathed, ingested, or applied to the skin at very high levels, they can be very harmful. Effects observed in people include irritation and burning of skin, eyes, mouth, and throat; abdominal pain and vomiting; heart damage; anemia; liver and kidney damage; facial paralysis; coma; and death. Breathing high levels of cresols for a short time results in irritation of the nose and throat. Aside from these effects, very little is known about the effects of breathing cresols, for example, at lower levels over longer times. Ingesting high levels results in kidney problems, mouth and throat burns, abdominal pain, vomiting, and effects on the blood and nervous system. Skin contact with high levels of cresols can burn the skin and damage the kidneys, liver, blood, brain, and lungs. (wikipedia). 108-39-4

342

C7H8O

108.057510 Colorless solids or liquids.

11.8°C

22.7 mg/mL at 25°C [YALKOWSKY,SH & HE,Y (2003)]

Oral (L528) ; inhalation (L528) ; dermal (L528)

m-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.

Cresols 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. (L528, A197, L529, A198) LD50: 242 mg/kg (Oral, Rat) (T13) LD50: 168 mg/kg (Intraperitoneal, Mouse) (T13) LD50: 2050 mg/kg (Dermal, Rabbit) (T13) No indication of carcinogenicity to humans (not listed by IARC).

Cresols are used to as solvents, disinfectants and deodorizers, as well as to make other chemicals. They may be formed normally in the body from other compounds. Cresols are found in many foods and in wood and tobacco smoke, crude oil, coal tar, and in chemical mixtures used as wood preservatives. Small organisms in soil and water produce cresols when they break down materials in the environment. Breathing air containing cresols is the primary source of exposure. Exposure may also result from drinking contaminated water, eating contaminated food and coming into contact with liquids containing cresols. (L528)

Intermediate Oral: 0.1 mg/kg/day (L134) Chronic Oral: 0.1 mg/kg/day (L134)

Acute 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.

Ingestion of cresols results in burning of the mouth and throat, abdominal pain, and vomiting. Inhalation or dermal exposure to cresols can produce irritation and corrosion at the site of contact. (L482) If 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.

2009-06-23T17:19:25Z

2014-12-24T20:24:43Z

Cytochrome P450 1A1 (P04798) Cytochrome P450 1A2 (P05177) Cytochrome P450 2C19 (P33261) Cytochrome P450 2D6 (P10635) Cytochrome P450 2E1 (P05181) Tyrosinase (P14679) Thyroid peroxidase (P07202) (L528)

http://en.wikipedia.org/wiki/m-Cresol

C01467

17231

CPD-112

C042041

Cresol, Meta-

DB01776

CRS

3506

true

CC1=CC(O)=CC=C1

C7H8O

InChI=1S/C7H8O/c1-6-3-2-4-7(8)5-6/h2-5,8H,1H3

InChIKey=RLSSMJSEOOYNOY-UHFFFAOYSA-N

108.1378

108.057514878

Endogenous Liquid 1.96

HMDB02048

CHEMBL298312

21105871

<p>Gerd Leston, “Preparation of 5-sec-alkyl-m-cresol.” U.S. Patent US3992455, issued September, 1963.</p>