72 Toluene Toluene is found in allspice. Toluene is isolated from distilled tolu balsam (Myroxylon balsamum). Minor constituent of lime oil (Citrus aurantifolia).Toluene, formerly known as toluol, is a clear, water-insoluble liquid with the typical smell of paint thinners. It is an aromatic hydrocarbon that is widely used as an industrial feedstock and as a solvent. (Wikipedia) Toluene has been shown to exhibit beta-oxidant, depressant, hepatoprotective, anesthetic and neurotransmitter functions (A7693, A7694, A7695, A7696, A7697). 108-88-3 1140 C7H8 92.062600 Colorless liquid. -95°C 110.6°C (231.1°F) 0.526 mg/mL at 25°C Oral (L174) ; inhalation (L174) ; dermal (L174) Toluene 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. Inhalation and ingestion are the primary routes of exposure, though toluene may also be absorbed through the skin. It accumulates rapidly in the brain and is subsequently deposited in other tissues according to their lipid content, with the highest levels attained in adipose tissue. The primary initial steps in toluene metabolism is side-chain hydroxylation catalyzed predominately by the cytochrome P450 isozyme CYP2E1, followed by oxidation to benzoic acid. Most of the benzoic acid is then conjugated with glycine to form hippuric acid, but a small portion can be conjugated with UDP-glucuronate to form the acyl-glucuronide. A very small portion of absorbed toluene can be converted by CYP1A2, CYP2B2, or CYP2E1 to ortho- or para-cresol. These metabolites are excreted in the urine, and the remaining toluene is exhaled unchanged. (T10, L174) LD50: 5000 mg/kg (Oral, Rat) (T14) LD50: 1332 mg/kg (Intraperitoneal, Rat) (T14) LD50: 1960 mg/kg (Intravenous, Rat) (T14) LD50: 2250 mg/kg (Subcutaneous, Mouse) (T14) LD50: 12 124 mg/kg (Dermal, Rabbit) (T14) LC50: 400 ppm over 24 hours (Inhalation, Mouse) (T14) 50 mg/kg for an adult human. (T26) 3, not classifiable as to its carcinogenicity to humans. (L135) Toluene is used in paints, paint thinners, fingernail polish, lacquers, adhesives, and rubber and in some printing and leather tanning processes. Gasoline, which contains 5 to 7 perfect toluene by weight, is the largest source of atmospheric emissions and exposure of the general populace. (T10, L174) Acute Inhalation: 1 ppm (L134) Chronic Inhalation: 0.08 ppm (L134) Acute Oral: 0.8 mg/kg/day (L134) Intermediate Oral: 0.02 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. The central nervous system is the primary target organ of toluene and other alkylbenzenes. Manifestations of exposure range from slight dizziness and headache to unconciousness, respiratory depression and death. Other symptoms include tiredness, confusion, weakness, memory loss, nausea, loss of appetite, and hearing and color vision loss. These symptoms usually disappear when exposure is stopped. (T10, L174) 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. 2009-03-06T18:58:01Z 2014-12-24T20:21:02Z Cytochrome P450 2E1 (P05181) Cytochrome P450 2B6 (P20813) Cytochrome P450 2C8 (P10632) Cytochrome P450 1A2 (P05177) Cytochrome P450 1A1 (P04798) (L174) http://en.wikipedia.org/wiki/Toluene C01455 17578 CPD-616 D014050 Toluene DB01900 MBN 1391 true Cytochrome P450 2E1 (P05181) Cytochrome P450 2B6 (P20813) Cytochrome P450 2C8 (P10632) Cytochrome P450 1A2 (P05177) Cytochrome P450 1A1 (P04798) (L174) CC1=CC=CC=C1 C7H8 InChI=1S/C7H8/c1-7-5-3-2-4-6-7/h2-6H,1H3 InChIKey=YXFVVABEGXRONW-UHFFFAOYSA-N 92.1384 92.062600256 Exogenous Liquid 2.73 HMDB34168 CHEMBL9113 1108 <p>Gregoire Kalopissis, Andree Bugaut, &#8220;2-Carbamylmethyl-or (diethylcarbamyl)methyl-amino-4-hydroxy toluene and process for preparing the same.&#8221; U.S. Patent US4101576, issued August, 1905.</p>