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Record Information
Version2.0
Creation Date2014-08-29 05:52:32 UTC
Update Date2014-12-24 20:26:42 UTC
Accession NumberT3D4202
Identification
Common NameCarbamic acid
ClassSmall Molecule
DescriptionCarbamic acid is occasionally found as carbamate in workers exposed to pesticides. Carbamates, particularly carbofuran, seem to be more associated with exuberant and diversified symptomatology of pesticide exposure than organophosphates. Neurological symptoms occur among farmers occupationally exposed to acetylcholinesterase-inhibiting insecticides such as carbamates. Carbamic acid products of several amines, such as beta-N-methylamino-L-alanine (BMAA), ethylenediamine, and L-cysteine have been implicated in toxicity. Studies suggested that a significant portion of amino-compounds in biological samples (that naturally contain CO2/bicarbonate) can be present as a carbamic acid. The formation of carbamate glucuronide metabolites has been described for numerous pharmaceuticals and they have been identified in all of the species commonly used in drug metabolism studies (rat, dog, mouse, rabbit, guinea pig, and human). There has been no obvious species specificity for their formation and no preference for 1 or 2 degree amines. Many biological reactions have also been described in the literature that involve the reaction of CO2 with amino groups of biomolecules. For example, CO2 generated from cellular respiration is expired in part through the reversible formation of a carbamate between CO2 and the -amino groups of the alpha and beta-chains of hemoglobin. Glucuronidation is an important mechanism used by mammalian systems to clear and eliminate both endogenous and foreign chemicals. Many functional groups are susceptible to conjugation with glucuronic acid, including hydroxyls, phenols, carboxyls, activated carbons, thiols, amines, and selenium. Primary and secondary amines can also react with carbon dioxide (CO2) via a reversible reaction to form a carbamic acid. The carbamic acid is also a substrate for glucuronidation and results in a stable carbamate glucuronide metabolite. The detection and characterization of these products has been facilitated greatly by the advent of soft ionization mass spectrometry techniques and high field NMR instrumentation. (1, 2, 3).
Compound Type
  • Amine
  • Animal Toxin
  • Cigarette Toxin
  • Food Toxin
  • Insecticide
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Pesticide
Chemical Structure
Thumb
Synonyms
Synonym
Aminoformate
Aminoformic acid
Carbamate
Carbamate ion
Chlorphenesin carbamate
Maolate
Chemical FormulaCH3NO2
Average Molecular Mass61.040 g/mol
Monoisotopic Mass61.016 g/mol
CAS Registry Number463-77-4
IUPAC Namecarbamic acid
Traditional Namecarbamic acid
SMILESNC(O)=O
InChI IdentifierInChI=1S/CH3NO2/c2-1(3)4/h2H2,(H,3,4)
InChI KeyInChIKey=KXDHJXZQYSOELW-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as organic carbonic acids and derivatives. Organic carbonic acids and derivatives are compounds comprising the organic carbonic acid or a derivative thereof.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassOrganic carbonic acids and derivatives
Sub ClassNot Available
Direct ParentOrganic carbonic acids and derivatives
Alternative Parents
Substituents
  • Carbonic acid derivative
  • Carbamic acid derivative
  • Carbamic acid
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Neuron
  • Placenta
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point153°C (307.4°F)
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility379.0 mg/mLALOGPS
logP-1.1ALOGPS
logP-0.56ChemAxon
logS0.79ALOGPS
pKa (Strongest Acidic)3.92ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area63.32 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity11.32 m3·mol-1ChemAxon
Polarizability4.68 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSsplash10-03di-9000000000-d4ec45366294deee461dView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS)splash10-00di-9200000000-39800d42e236043754c2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-9000000000-33c2cd9e9f87e70aeee7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03dl-9000000000-80dc946b5f814bf962fcView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-db68c8dff28932d0bd97View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03dl-9000000000-54e827d7f4201ae683bfView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03dl-9000000000-3158c8b265d264989bd7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-24350f23db0893ec042cView in MoNA
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityCarbamic acid 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.
MetabolismParaoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of OP exposure.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThis is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.
Minimum Risk LevelNot Available
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.
SymptomsSymptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include 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. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.
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 IDDB04261
HMDB IDHMDB03551
PubChem Compound ID277
ChEMBL IDCHEMBL125278
ChemSpider ID271
KEGG IDC01563
UniProt IDNot Available
OMIM ID
ChEBI ID28616
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDOUT
ACToR IDNot Available
Wikipedia LinkCarbamic acid
References
Synthesis Reference

Werner Daum, “Preparation of benzimidazol-2-yl-carbamic acid alkyl esters.” U.S. Patent US3933846, issued May, 1939.

MSDSLink
General References
  1. Rendon von Osten J, Epomex C, Tinoco-Ojanguren R, Soares AM, Guilhermino L: Effect of pesticide exposure on acetylcholinesterase activity in subsistence farmers from Campeche, Mexico. Arch Environ Health. 2004 Aug;59(8):418-25. [16268118 ]
  2. Schaefer WH: Reaction of primary and secondary amines to form carbamic acid glucuronides. Curr Drug Metab. 2006 Dec;7(8):873-81. [17168688 ]
  3. Smit LA, van-Wendel-de-Joode BN, Heederik D, Peiris-John RJ, van der Hoek W: Neurological symptoms among Sri Lankan farmers occupationally exposed to acetylcholinesterase-inhibiting insecticides. Am J Ind Med. 2003 Sep;44(3):254-64. [12929145 ]
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
IC5067 uMNot AvailableBindingDB 50369454
References
  1. Houghten RA, Pinilla C, Appel JR, Blondelle SE, Dooley CT, Eichler J, Nefzi A, Ostresh JM: Mixture-based synthetic combinatorial libraries. J Med Chem. 1999 Sep 23;42(19):3743-78. [10508425 ]