| | Nicotine Chemical Properties |
| Melting point | -80 °C | | alpha | -166 º (c=neat) | | Boiling point | 243-248 °C | | density | 1.010 g/mL at 20 °C(lit.) | | vapor pressure | 0.06 hPa (20 °C) | | refractive index | n20/D 1.5265(lit.) | | Fp | 215 °F | | storage temp. | 2-8°C | | solubility | ethanol: 50 mg/mL | | pka | 8.02(at 25℃) | | form | liquid | | color | yellow | | PH | 10.2 (8.1g/l, H2O, 20°C) | | Odor Threshold | 0.011ppm | | optical activity | [α]20/D 169°(lit.) | | explosive limit | 0.7-4%(V) | | Water Solubility | MISCIBLE | | Sensitive | Air Sensitive & Hygroscopic | | Merck | 14,6524 | | BRN | 82109 | | Exposure limits | TLV-TWA air 0.5 mg/m3 (ACGIH, MSHA,
and OSHA). | | LogP | 1.170 | | CAS DataBase Reference | 54-11-5(CAS DataBase Reference) | | NIST Chemistry Reference | 3-(2-(N-methylpyrrolidinyl))pyridine(54-11-5) | | EPA Substance Registry System | Nicotine (54-11-5) |
| | Nicotine Usage And Synthesis |
| alkaloid | Nicotine is the substance in tobacco, nicotine content of tobacco because there are different species and origin, alkali content of tobacco each part is different. Cigarette factory scraps (tobacco powder) containing about 1% to 2% of the nicotine, tobacco stems and ribs smoke nicotine containing about 1% or so, people smoked cigarette contains nicotine amounted to about 3%. Pure nicotine is a colorless, oily liquid, miscible with water below 60 ℃, hydrate, more than 210 ℃ also miscible with water. Unstable nature, likely to be volatile, soluble in water and organic solvents. Nicotine is an alkaloid, so all properties of a base, to a compound made of salts and acids. In case of light and air turn brown and sticky, there is the odd smell and strong irritant. | | Toxicity | Pure nicotine for people, livestock highly toxic rat oral LD50 of 50~60mg/kg, rabbit acute percutaneous LD5050mg/kg.
Rabbit acute percutaneous LD50 for 50~60mg/kg, rabbit acute oral LD50 of 50mg/kg. Based on China's pesticide toxicity
grading standards, is a highly toxic pesticides. However, because of volatile and rapidly decompose in air and light, and
therefore can still be used to control pests on crops. Rapidly absorbed through the skin, inhalation and dermal exposure to
toxic people. Toxic to birds. Young steelhead LC504mg/L, toxic to bees, but there insecticide effect. D. Pulex LC50 of
0.24mg/L. Fish and shellfish toxicity, mild injury to crops.
| | Description | (–)-Nicotine is an alkaloid that has been found in tobacco. It is an agonist at neuronal nicotinic acetylcholine receptors (nAChRs) and binds to α3β4 and α4β2 subunit-containing nAChRs with Ki values of 481 and 11.1 nM, respectively. Chronic exposure to (–)-nicotine results in increased expression of certain nAChRs, particularly α4β2 subunit-containing nAChRs. (–)-Nicotine has addictive properties. Formulations containing (–)-nicotine have been used as smoking cessation aids for the relief of nicotine withdrawal symptoms. | | Description | Nicotine is an alkaloid obtained from the dried leaves
of Nicotiana tabacum and Nicotiana rustica. Nicotine
stimulates acetylcholine receptors of the postsynaptic
membrane at nerve synapses resulting in depolarization
of the membrane. Toxic doses cause stimulation that is
rapidly followed by blockade of nerve transmission. | | Chemical Properties | Yellow Liquid | | Chemical Properties | Nicotine is a pale yellow to dark brown, oily
liquid. Slight, fishy or pyridine-like odor when warm. It is
also available as a powder. | | Originator | Nicotinell TTS,Novartis | | Uses | Nicotine is one of the principal constituentsof tobacco. It occurs in the dried leavesof Nicotiana tabacum and Nicotiana rusticato the extent of 2–8%. Exposure risk tothis alkaloid arises from smoking, chewing,or inhaling tobacco. Nicotine and its saltsare used as insecticides and fumigants, intanning, and in medicine. | | Uses | Nicotine is the second most widely used recreational drug after caffeine. At low doses, nicotineacts as a stimulant to the central nervous system by activating acetylcholine receptors, specifically called nicotinic acetylcholine receptors, in the postsynaptic neurons during nerve transmission.At higher doses nicotine acts as a depressant.Nicotine in tobacco has always been used for medicinal purposes. Nicotine solutions made from soaking tobacco leaves in water have been used as pesticides for several hundred years. In modern times, numerous pharmaceutical companies have explored nicotine's use for treating diseases. Nicotine's most prevalent medicinal use is for smoking cessation in the form of alternate delivery systems such as gums and dermal patches. Nicotine is used medically for numerous conditions and its use is being explored in additional areas including pain relievers, attention deficit disorder medications and medications associated with Alzheimer's disease, Parkinson disease, colitis, herpes, and tuberculosis. | | Uses | Naturally-occuring isomer | | Uses | Prototype nicotinic acetylcholine receptor agonist; naturally occurring isomer.
| | Uses | (S)-(-)-Nicotine is a prototype nicotinic acetylcholine receptor agonist. (S)-(-)-Nicotine is the naturally occurring isomer. Nicotine can be absorbed through the alimentary canal, respiratory tract and intact skin. Nicotine is used in the treatment of smoking withdrawal syndrome. Nicotine has been used as an anthelmintic.
| | Definition | ChEBI: An optically active form of nicotine having S-configuration. | | Definition | A colourless poisonousalkaloid present in tobacco. It isused as an insecticide. | | Production Methods | The nicotine molecule consists of a pyrrolidine ring attached to a pyridine ring by a bondbetween carbon atoms in the two-ring systems. Nicotine was isolated in impure form fromtobacco in 1809 by Louis Nicholas-Vauquelin (1763–1829). Vauquelin called the substancenicotianine. In 1826, Wilhelm Posselt (1806–1877) and Karl Ludwig Reimann (1804–1872),medical students at Heidelberg University, isolated pure nicotine and published dissertationson its pharmacology in 1828. Louis Henri Melsens (1814–1886) determined nicotine’sempirical formula. Amé Pictet (1857–1937) and P. Crépieux reported the synthesis of nicotine in 1903. | | Manufacturing Process | The water extract from Nicotiana tabacum was prepared by distillation of
nicotine contained liquor from tobacco leaves, as described in D.R. Patent No.
319,846; September 12, 1913.
5 kg this water extract or the same quantity of tobacco powder in water was
mixed with 1.5 kg of grinded calcium hydroxide and 1.5 kg calcium sulfate.
The mixture stood for 24 hours. The obtained mixture looked like a dry
powder. It was extracted with ether. The ether was distilled and the residue
contented 98% of clear nicotine - liquid with odor of pyridine; BP: 246C/735
mm; d4
20 =1.0097; [α]d
20=- 166.5. | | Brand name | Habitrol (Novartis); Nicoderm (Sanofi Aventis); Nicotrol
(Pharmacia & Upjohn); Prostep (Aveva). | | Therapeutic Function | Ganglion depressant, Smoking deterrent | | General Description | Liquids. Toxic by inhalation, ingestion, and skin absorption. More dense than water. Flash points usually below 140°F. Contact may irritate skin, eyes, and mucous membranes. If available, obtain the technical name of the material from the shipping papers and contact CHEMTREC, (800-424-9300) for specific response information. | | Air & Water Reactions | Flammable. Slightly soluble in water. | | Reactivity Profile | An alkaloid produced from tobacco. Colorless, oily liquid, combustible, highly toxic. When heated to decomposition L-Nicotine emits very toxic fumes of carbon monoxide and oxides of nitrogen [Lewis, 3rd ed., 1993, p. 919]. | | Hazard | Toxic by ingestion, inhalation, and skin
absorption. Gastrointestinal damage, central nervous system impairment, and cardiac impairment | | Health Hazard | Nicotine is a highly toxic compound. It stimulatesneuromuscular junctions and nicotinicreceptors, causing depression and paralysisof autonomic ganglia. Exposure routesare ingestion, absorption through skin, orinhalation (smoking or inhaling tobacco).The acute toxic symptoms in humansinclude nausea, vomiting, salivation, muscularweakness, twitching, and convulsions.The symptoms of confusion, hallucinations,and distorted perceptions have also beennoted in humans. Death may occur from respiratoryfailure. The lethal dose is approximately40 mg/kg. Chronic poisoning fromoccupational exposure may exhibit symptomsof vomiting and diarrhea. Fatal casesdue to occupational poisoning are unusual.
Nicotine administered in animals producedtoxic symptoms that include somnolence,change in motor activity, ataxia, dyspnea,tremor, and convulsions.
LD50 values, intraperitoneal (rats): 14.5 mg/kgLD50 values, oral (rats): 50 mg/kg
Kramer and coworkers (1989) investigatedthe effect of nicotine on the accumulation ofdopamine in synaptic vesicles prepared frommouse cerebral cortex or bovine striatum. Itwas found to be a weak inhibitor of dopamineaccumulation.
The role of nicotine in tobacco carcinogenesisis not yet fully understood. Nicotine is a precursor of N0-nitrosonornicotine , which is asuspected lung carcinogen (Hoffmann et al.1985). Nicotine-derived N-nitrosoaminescontribute significantly to carcinogenesiscaused by tobacco. However, there is noevidence in animals or humans of cancerscaused by nicotine itself. Berger and coworkers(1987) have found a beneficial effect ofperinatal nicotine administration in decreasingthe tumors of the neuorogenic systeminduced by N-methylnitrosourea in Sprague-Dawley rats. Although nicotineis noncarcinogenic, it acts as a cofactorin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene in male Syrian goldenhamsters (Chen and Squier 1990).
Nicotine produced teratogenic effects intest animals, causing postimplantation mortality,fetal death, and developmental abnormalities.Nicotine and its primary metabolitecotinine exhibited teratogenic potential withXenopus frog embryo teratogenesis assay(Dowson et al. 1988).
Nicotine tested negative in the Neurosporacrassa –aneuploidy and histidinereversion–Ames tests for mutagenicity. | | Health Hazard | L-Nicotine is classified as super toxic. Probable oral lethal dose in humans is less than 5 mg/kg or a taste (less than 7 drops) for a 70 kg (150 lbs.) person. It may be assumed that ingestion of 40-60 mg of nicotine is lethal to humans. There is fundamental difference between acute toxicity from use of nicotine as insecticide or from ingestion, and chronic toxicity that may be caused by prolonged exposure to small doses as occurs in smoking. Maternal smoking during pregnancy is associated with increased risk of spontaneous abortion, low birth weight and still-birth. Nicotine was found as a co-carcinogen in animals. | | Fire Hazard | There is a moderate explosion hazard when exposed to heat or flame. When heated to decomposition, L-Nicotine emits nitrogen oxides, carbon monoxide and other highly toxic fumes. Avoid oxidizing materials. Stable under normal conditions. Avoid heat or flames. | | Agricultural Uses | Insecticide: Nicotine is used in some drugs and insecticides.
Classified for restricted use as an insecticide, limited to use
by or under the direct supervision of a certified applicator.
Not listed for use in EU countries. Registered for use in
the U.S. and Canada. A U.S. EPA restricted Use Pesticide
(RUP). | | Trade name | BLACK LEAF®; CAMPBELL'S NICOSOAP
®; DESTRUXOL ORCHARD SPRAY®; EMONIB
®; FLUX MAAG®; FUMETO-TENDUST®; BAC®;
MACH-NIC®; NIAGARA P. A. DUST®; NICODUST®;
NICOFUME®; NICOCIDE®; ORTHO N-4 DUST®; XL
ALL INSECTICIDE® | | Potential Exposure | An alkaloid produced from tobacco.
Nicotine is used in some drugs; and in tanning. At one
time, nicotine was used in the United States as an insecticide
and fumigant; however, it is no longer produced or
used in the United States for this purpose. | | Carcinogenicity | Nicotine has low carcinogenic
potential. One study found that diets containing
60 ppm nicotine and administered to rats for 300 days
reduced the growth rate. The authors concluded that reduced
body weight gains were only partially attributable to reduced
food intake. No pathology on the rats and no evidence of
carcinogenicity were reported. Rats were injected subcutaneously
(5 days/week) for 26 weeks followed by an approximate
2-month observation period. Similarly, dogs were
injected subcutaneously (5 days/week) for the same period.
No tumors were observed in the test animals, although
hyaline thickening and fibrosis of the vasculature of the
kidney, lung, brain, and heart were evident. | | Metabolic pathway | Nicotine has been used as an insecticide for at least 200 years but this
naturally occurring compound lacks persistence and can be hazardous in
use (Corbett et al., 1984). It has been replaced with more effective synthetic
insecticides such as those in the neonicotinoid class. Most of the mformation
on metabolism derives from research into the fate of nicotine after
tobacco smoking as well as from the use of nicotine in agriculture and
horticulture or through the biosynthesis of the alkaloid by plants and
vegetables used as normal foodstuffs. Up to eight metabolites have been
isolated and identified in man with six primary pathways. The main
pathway is N-carbon oxidation of the pyrrolidine ring to form cotinine,
others being N-oxidation of the pyrrolidine ring to form nicotine N-oxide,
N-methylation of the pyridine ring to form an N-methylnicotinium ion
and N-demethylation of the pyrrolidine ring to form nornicotine. Two
other pathways are formation of a nicotine enamhe and of a nicotine
glucuronide (Gabrielsson and Gumbleton, 1993). There is little information
on the fate of nicotine in soil. | | Metabolism | Nicotine is well absorbed from the mucous membranes
in the oral cavity, gastrointestinal tract, and respiratory
system. If tobacco smoke is held in the mouth for 2 seconds,
66 to 77% of the nicotine in the smoke will be absorbed
across the oral mucosa. If tobacco smoke is inhaled,
approximately 90 to 98% of the nicotine will be
absorbed. Nicotine is distributed throughout the body,
readily crossing the blood-brain and placental barriers.
The liver, kidney, and lung metabolize approximately 80
to 90% of the alkaloid. The kidney rapidly eliminates
nicotine and its metabolites. | | Shipping | UN1654 Nicotine, Hazard Class: 6.1; Labels:
6.1-Poisonous materials. | | Purification Methods | (-)-Nicotine is a very pale yellow hygroscopic oil with a characteristic odour (tobacco extract) which turns brown in air on exposure to light. It is purifed by fractional distillation under reduced pressure in an inert atmosphere. A freshly distilled sample should be stored in dark sealed containers under N2. It is a strong base; a 0.05 M aqueous solution has a pH of 10.2. It is very soluble in organic solvents. It is soluble in H2O and readily forms salts. [UV: Parvis J Chem Soc 97 1035 1910, Dobbie & Fox J Chem Soc 103 1194 1913.] The hydrochlorides (mono-and di-) form deliquescent crystals soluble in H2O and EtOH but insoluble in Et2O. It has also been purified via the ZnCl2 double salt. [Ratz Monatsh Chem 26 1241 1905, Biosynthesis: Nakan & Hitchinson J Org Chem 43 3922 1978.] The picrate has m 218o (from EtOH). [Beilstein 23/6 V 64.] POISONOUS. | | Degradation | Nicotine is volatile and decomposes relatively quickly under the influence
of light and air. The pyrrolidine nitrogen (pka 8.2) is more basic than the
pyridine moiety (pka 3.1) (PM). Nicotine has a chiral centre, and exists
naturally as the more potent (S) enantiomer. | | Incompatibilities | Incompatible with strong oxidizers (chlorates,
nitrates, peroxides, permanganates, perchlorates,
chlorine, bromine, fluorine, etc.); contact may cause fires
or explosions. Keep away from alkaline materials, strong
bases, strong acids, oxoacids, epoxides. Incompatible with
strong acids. Attacks some forms of plastics, rubber, and
coatings. | | Waste Disposal | Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator
equipped with an afterburner and scrubber. All federal,
state, and local environmental regulations must be
observed. In accordance with 40CFR165, follow
recommendations for the disposal of pesticides and pesticide
containers. Must be disposed properly by following
package label directions or by contacting your local or
federal environmental control agency, or by contacting
your regional EPA office. Consult with environmental
regulatory agencies for guidance on acceptable disposal
practices. Generators of waste containing this contaminant
(≥100 kg/mo) must conform with EPA regulations
governing storage, transportation, treatment, and waste
disposal. | | References | Pictet, Rotschy., Ber., 33, 2533 (1900)
Tschitschibabin, Buchholz.,J. Russ. Phys. Chern. Soc., 50, 548 (1920)
Spath, Biniecki., Ber., 72, 1809 (1939)
Shmuk, Borozdina., CampI. rend. Acad. Sci., USSR, 12,1582 (1939)
Shmuk, Borozdina., J. Appl. Chern. Russ., 14,864 (1941)
Smith, Smith., J. Agric. Res., 65, 347 (1942)
Pal, Narasinham.,!. Ind. Chern. Soc., 20, 181 (1943)
Marion., Can. J. Res., 23B, 165 (1945)
Bottomley, Nottle, White., Austral. J. Sci., 8, 18 (1945)
Biosynthesis:
Leete.,!. Amer. Chern. Soc., 89,7081 (1967)
14C-NMR spectrum:
Ganz, Kelsey, Geiling., Bot. Gaz., 113, 195 (1951)
13C-NMR spectrum:
Crain, Wilderman, Roberts., J. Amer. Chern. Soc., 93,990 (1971)
Pharmacology :
Rolleston., Lancet., 210,961 (1926)
Laessing., Med. Welt., 12, 1485 (1938)
Coon, Rothman., Proc. Soc. Exp. Bioi. Med., 42, 231 (1939)
Straub, Amann., Klin. Woch., 19,169 (1940)
Coon, Rothman., J. Pharm. Exp. Ther. Froc., 72, 9 (1941)
Perlman, Dannesborg, Sokoloff., J. Amer. Med. Assoc., 120, 1003 (1942)
Roth, McDonald, Sheard., ibid, 125,761 (1944)
Burn, Truelove, Burn., Brit. Med. J., i, 403 (1945) |
| | Nicotine Preparation Products And Raw materials |
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