Canmetcon
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Record Information
Version2.0
Creation Date2009-06-11 18:07:52 UTC
Update Date2014-12-24 20:22:53 UTC
Accession NumberT3D0864
Identification
Common Nameo-Xylene
ClassSmall Molecule
DescriptionO-xylene is an aromatic hydrocarbon based on benzene with two methyl substituents. It is a isomer of xylene. Xylene occurs naturally in petroleum and coal tar, and is major component of gasoline and fuel oil. Xylene is used mainly as a solvent and in the printing, rubber, and leather industries. O-xylene is largely used in the production of phthalic anhydride, and is generally extracted by distillation from a mixed xylene stream in a plant primarily designed for p-xylene production. Contrary to popular belief, a series of switch condensers is required, and not a complicated setup of distillation columns that never work (10, 5, 8). It can cause irritation eyes, skin, nose, throat; dizziness, excitement, drowsiness, incoordination, staggering gait; corneal vacuolization; anorexia, nausea, vomiting, abdominal pain; dermatitis. The targets of this compound are eyes, skin, respiratory system, central nervous system, gastrointestinal tract, blood, liver, kidneys.
Compound Type
  • Aromatic Hydrocarbon
  • Food Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Lachrymator
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Pollutant
  • Solvent
Chemical Structure
Thumb
Synonyms
Synonym
1,2-dimethylbenzene
1,2-Dimethylbenzol
1,2-xylene
2-xylene
3,4-xylene
o-Dimethylbenzene
o-Methyltoluene
O-Xylene
o-Xylol
ORTHO-XYLENE
Chemical FormulaC8H10
Average Molecular Mass106.165 g/mol
Monoisotopic Mass106.078 g/mol
CAS Registry Number95-47-6
IUPAC Name1,2-xylene
Traditional Nameortho-xylene
SMILESCC1=CC=CC=C1C
InChI IdentifierInChI=1S/C8H10/c1-7-5-3-4-6-8(7)2/h3-6H,1-2H3
InChI KeyInChIKey=CTQNGGLPUBDAKN-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as o-xylenes. These are aromatic compounds that contain a o-xylene moiety, which is a monocyclic benzene carrying exactly two methyl groups at the 1- and 2-positions.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassXylenes
Direct Parento-Xylenes
Alternative Parents
Substituents
  • O-xylene
  • Aromatic hydrocarbon
  • Unsaturated hydrocarbon
  • Hydrocarbon
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceColorless liquid.
Experimental Properties
PropertyValue
Melting Point-25.2°C
Boiling PointNot Available
Solubility0.178 mg/mL at 25°C [SANEMASA,I et al. (1982)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.205 mg/mLALOGPS
logP3.16ALOGPS
logP3ChemAxon
logS-2.7ALOGPS
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity36.14 m3·mol-1ChemAxon
Polarizability12.95 Å3ChemAxon
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)splash10-0006-9200000000-91162619463de43f7b46View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-052f-9300000000-7444c78cfa46f8a9a90eView in MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0a4i-0900000000-f15325822f4f50e0f099View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0006-9200000000-91162619463de43f7b46View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-052f-9300000000-7444c78cfa46f8a9a90eView in MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0a4i-0900000000-f15325822f4f50e0f099View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-7900000000-392b6abb89b281539432View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0900000000-7dfff6875bd00f609d90View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-1900000000-89860e0d53bc8dcf7d90View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0kbf-9100000000-c253aaa68babc1381810View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0900000000-f15589460cfaed631148View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0900000000-f15589460cfaed631148View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-8900000000-a4303e6414e4609396f5View in MoNA
MSMass Spectrum (Electron Ionization)splash10-052f-9300000000-9030a9b0de39df7365ccView in MoNA
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
Toxicity Profile
Route of ExposureOral(8) ; inhalation (8) ; dermal (8)
Mechanism of Toxicityo-Xylene 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.
MetabolismXylenes are well absorbed by the inhalation and oral routes. Approximately 60% of inspired xylene is retained and approximately 90% of ingested xylene is absorbed. Absorption also occurs by the dermal route, but to a much lesser extent than by the inhalation and oral routes. Following absorption, xylene is rapidly distributed throughout the body by way of the systemic circulation. In the blood, it is primarily bound to serum proteins and accumulates primarily in adipose tissue. Xylene is primarily metabolized by oxidation of a methyl group and conjugation with glycine to yield the methylhippuric acid, whicih is the primary metabolite excreted in urine. Aromatic hydroxylation of xylene to xylenol occurs to only a limited extent in humans. Less than 2% of an absorbed dose is excreted in the urine as xylenol. Other minor metabolites found in urine include methylbenzyl alcohol and glucuronic acid conjugates of the oxidized xylene. In humans, hepatic microsomal CYP2E1 is the primary enzyme involved with the metabolism of xylene to methylbenzylalcohol, the dominant pathway leading to the formation of methylhippuric acid isomers. Unmetabolized xylene can be exhalated or also excreted in urine. (8)
Toxicity ValuesLD50: 4595 ppm (Inhalation, Mouse) (8)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (7)
Uses/SourcesXylene is used as a solvent and in the printing, rubber, and leather industries. It is also used as a cleaning agent, a thinner for paint, and in paints and varnishes. It is found in small amounts in airplane fuel and gasoline. Exposure to xylene may occur from breathing it in contaminated air, drinking or eating xylene-contaminated water or food, and through dermal and eye contact with xylene containing products. (8, 8)
Minimum Risk LevelAcute Inhalation: 2 ppm (8) Intermediate Inhalation: 0.6 ppm (8) Chronic Inhalation: 0.05 ppm (8) Acute Oral: 1 mg/kg/day (8) Intermediate Oral: 0.4 mg/kg/day (8) Chronic Oral: 0.2 mg/kg/day (8)
Health EffectsAcute 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.
SymptomsDizziness, drowsiness, headache, and nausea can follow ihnalation and ingestion exposure. Burning sensations and abdominal pain can also result from ingestion. Dry skin, redness, and pain can result from dermal and eye exposure depending on the route of exposure. Conjunctivitis, dermatitis, irritation to respiratory tract, dyspnea, anorexia, vomiting, fatigue, vertigo, incoordination, irritation, gangrene and anemia can also follow xylene poisoning. (1)
TreatmentIf 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.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB03029
HMDB IDHMDB59851
PubChem Compound ID7237
ChEMBL IDNot Available
ChemSpider ID6967
KEGG IDC07212
UniProt IDNot Available
OMIM ID
ChEBI ID28063
BioCyc IDNot Available
CTD IDNot Available
Stitch IDXylene, ortho-
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis Reference

George E. Kuhlmann, Alan G. Bemis, “Preparation of phthalic acid by solventless oxidation of liquid ortho-xylene.” U.S. Patent US4299977, issued November, 1975.

MSDST3D0864.pdf
General References
  1. Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E: Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46. Epub 2004 Nov 10. [15537682 ]
  2. Han QJ, Wu HL, Cai CB, Tang LJ, Yu RQ: Using near-infrared spectroscopy and differential adsorption bed method to study adsorption kinetics of orthoxylene on silica gel. Talanta. 2008 Aug 15;76(4):752-7. doi: 10.1016/j.talanta.2008.04.021. Epub 2008 Apr 20. [18656653 ]
  3. Silaev MM: [New kinetic model of the radical-chain oxidation, including competitive reactions: oxygen as an autoinhibitor]. Biofizika. 2001 Mar-Apr;46(2):203-9. [11357330 ]
  4. van Beelen P, Fleuren-Kemila AK: Toxic effects of pentachlorophenol and other pollutants on the mineralization of acetate in several soils. Ecotoxicol Environ Saf. 1993 Aug;26(1):10-7. [7691530 ]
  5. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
  6. ITII (1982). Toxic and Hazarous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute.
  7. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  8. ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for xylene. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  9. International Programme on Chemical Safety (IPCS) INCHEM (1992). Poison Information Monograph for Xylene. [Link]
  10. Wikipedia. P-Xylene. Last Updated 19 July 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Serine hydrolase activity
Specific Function:
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name:
ACHE
Uniprot ID:
P22303
Molecular Weight:
67795.525 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC504.9 uMNot AvailableBindingDB 50008560
References
  1. Cardozo MG, Iimura Y, Sugimoto H, Yamanishi Y, Hopfinger AJ: QSAR analyses of the substituted indanone and benzylpiperidine rings of a series of indanone-benzylpiperidine inhibitors of acetylcholinesterase. J Med Chem. 1992 Feb 7;35(3):584-9. [1738151 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular Weight:
56848.42 Da
References
  1. Foy JW, Silverman DM, Schatz RA: Low-level m-Xylene inhalation alters pulmonary and hepatic cytochrome P-450 activity in the rat. J Toxicol Environ Health. 1996 Feb 9;47(2):135-44. [8598570 ]
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP4B1
Uniprot ID:
P13584
Molecular Weight:
58990.64 Da
References
  1. Foy JW, Silverman DM, Schatz RA: Low-level m-Xylene inhalation alters pulmonary and hepatic cytochrome P-450 activity in the rat. J Toxicol Environ Health. 1996 Feb 9;47(2):135-44. [8598570 ]
General Function:
Temperature-gated cation channel activity
Specific Function:
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
Gene Name:
TRPA1
Uniprot ID:
O75762
Molecular Weight:
127499.88 Da
References
  1. Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]