Methacrylonitrile

Last updated
Methacrylonitrile
Methacrylonitrile skeletal.svg
Methacrylonitrile.svg
Names
Preferred IUPAC name
2-Methylprop-2-enenitrile
Other names
Methylacrylonitrile
2-Cyanopropene
2-Cyano-1-propene
Isopropenecyanide
Isopropenylcyanid
Isopropene cyanide
Identifiers
3D model (JSmol)
AbbreviationsMeAN
ChEMBL
ChemSpider
ECHA InfoCard 100.004.380 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 204-817-5
PubChem CID
RTECS number
  • UD1400000
UNII
UN number 3079
  • InChI=1S/C4H5N/c1-4(2)3-5/h1H2,2H3
    Key: GYCMBHHDWRMZGG-UHFFFAOYSA-N
  • C=C(C)C#N
Properties
C4H5N
Molar mass 67.091 g·mol−1
AppearanceClear colorless to very slightly yellow liquid
Odor Bitter almonds [1]
Density 0.8 g/mL
Melting point −35.8 °C (−32.4 °F; 237.3 K)
Boiling point 90 to 92 °C (194 to 198 °F; 363 to 365 K)
2.57 g/100 mL (20 °C)
Vapor pressure 71 mmHg (25 °C) [1]
Hazards
GHS labelling:
GHS-pictogram-flamme.svg GHS-pictogram-skull.svg GHS-pictogram-exclam.svg
Danger
H225, H301, H311, H317, H331
P210, P233, P240, P241, P242, P243, P261, P264, P270, P271, P272, P280, P301+P310, P302+P352, P303+P361+P353, P304+P340, P311, P312, P321, P322, P330, P333+P313, P361, P363, P370+P378, P403+P233, P403+P235, P405, P501
Flash point 13 °C (55 °F; 286 K)
Explosive limits 2%-6.8% [1]
NIOSH (US health exposure limits):
PEL (Permissible)
none [1]
REL (Recommended)
TWA 1 ppm (3 mg/m3) [skin] [1]
IDLH (Immediate danger)
N.D. [1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Methacrylonitrile (or 2-Methylprop-2-enenitrile), MeAN in short, is a chemical compound that is an unsaturated aliphatic nitrile, widely used in the preparation of homopolymers, copolymers, elastomers, and plastics and as a chemical intermediate in the preparation of acids, amides, amines, esters, and other nitriles. MeAN is also used as a replacement for acrylonitrile in the manufacture of an acrylonitrile/butadiene/styrene-like polymer. It is a clear and colorless (to slightly yellow) liquid, that has a bitter almond smell. [2]

Contents

It is toxic by ingestion, inhalation, and skin absorption. [3]

Exposure and regulation

Since MeAN is present in polymeric coating materials as found in many everyday use items, humans are exposed to it by skin absorption. Aside from this there is an occupational exposure, and low levels of MeAN are also present in the smoke of unfiltered cigarettes made from air-cured or flue-cured tobaccos. [4]

Due to the toxicity of MeAN, the U.S. Department of Health & Human Services has limited the concentration of methacrylonitrile-derived polymer in resinous and polymeric coating materials to 41%. Its use in food packaging is further limited to 0.5 mg per square inch of food-contact surface, and only 50 ppm, or 0.005% MeAN is permitted in chloroform-soluble coating components in water containers (21 CFR, § 175.300). A time-weighted average (TWA) threshold limit value of 1 ppm (3 mg/m3) for MeAN exposure was adopted by the American Conference of Governmental Industrial Hygienists. [2] [5]

The National Cancer Institute (USA) nominated MeAN for research because of its potential for human exposure, the common features shared with the known carcinogen acrylonitrile and the shortcoming of knowledge in toxicity and carcinogenicity of MeAN. [2]

Structure and reactivity

Methacrylonitrile is an acrylonitrile (AN) with an additional CH3 group on the second carbon. Polymerization does not require a catalyst and happens rapidly in the absence of a stabilizer.

Because of its double bond, additional reactions are possible with biological molecules. The extra methyl group of MeAN lessens the electron-withdrawing effect caused by the nitrile so that reactions that form negative charge on the alpha carbon are faster with AN as the reactant. Inversely, reactions that form a positive charge on said carbon (i.g. Cytochrome-P450 oxidation of the double bond), are faster with MeAN as the reactant. As a result, in metabolism, MeAN conjugates less with glutathione (GSH) than AN, and is activated more easily. [5] [6]

Synthesis

Poly(acrylonitrile) is generally made via emulsion or solution polymerization. The commercial product can be stabilized by the addition of 50 ppm hydroquinone monoethyl ether. The polymerization of MeAN is carried out in tetrahydrofuran (THF) with the disodium salt of polyethylene oxide (PEO). MeAN is also commercially produced by the vapor-phase reaction of isobutylene with ammonia and oxygen in the presence of a catalyst. Acetonitrile, hydrogen cyanide and acrolein are known by-products. It is used in the preparation of homo- and copolymers, elastomers, coatings and plastics. It can be used as a replacement for acrylonitrile in similar reactions. MeAN can also be synthesized by dehydration of methacrylamide or from isopropylene oxide and ammonia. [7] [5]

Reactions

MeAN can undergo electropolymerization, if it is submitted to electroreduction at metallic cathodes in an organic anhydrous medium, for example; acetonitrile. There are two types of polymers that can be obtained at the end of the synthesis; a physisorbed polymer and a grafted polymer. The mechanism accounting for the non-grafted polymer is pretty well understood: it proceeds via the formation of a radical anion (the product of reduction of the vinylic monomer), which dimerizes in solution because of a radical–radical coupling mechanism (RRC) to deliver a di-anion acting as the initiator of a polymerization reaction in solution. [7]

Metabolism

There are different metabolizing pathways for methacrylonitrile, that are elaborated here:

First of all, methacrylonitrile can be directly conjugated with GSH, which leads to the formation of S-(2-cyanopropyl) GSH, which can be metabolized to N-acetyl-S- (2-cyanopropyl) cysteine (NACPC), which can be excreted in the urine. [5]

Due to this, glutathione is depleted to certain degrees after MeAN exposure. After oral exposure to 100 mg/kg MeAN in rats, the maximum depletion was noticed in the liver at 39% of control. This depletion, however, is less than found after AN administration. This is likely because MeAN exists in part bound to red blood cells, and is therefore unavailable for GSH conjugation. Studies using radiolabeled carbon point out that the primary route by which methacrylonitrile left the body is the urine, at 43% of the dose. An additional 18% is excreted in faeces (15%) and exhaled air (2.5%). This means that about 40% of MeAN does not leave the body immediately and is either bound to macromolecules or forms unexcretable conjugates. The red blood cells retained significant amounts of radioactivity: more than 50% of the radioactivity in erythrocytes was detected as covalently bound to hemoglobin and membrane proteins. [8] [9]

Secondly, methacrylonitrile can be metabolised in the liver by CYP2E1 (a Cytochrome-P450 enzyme). This is the most important enzyme for the oxidative metabolism, but also other cytochrome P-450 enzymes may be involved. The oxidative reaction by Cytochrome-P450 enzymes will lead to the formation of an epoxide intermediate, which shows reactivity. This epoxide intermediate is highly unstable and could lead to the formation of cyanide via different transformations. For example, via epoxide hydratase (EH) or via interactions with a sulfhydryl compound, which leads to the formation of a cyanohydrin that could rearrange to an aldehyde and thereby can possibly result in cyanide release. The epoxide can also be conjugated with GSH. [10] [11]

It has been shown that treatment of mice with carbon tetrachloride, which acts on the mixed function oxygenase system, results in much lower cyanide concentrations than controls and greatly reduced toxicity of MeAN, indicating that cyanide production is indeed the main pathway of toxicity, unlike AN, which is more carcinogenic. [5] More information about toxicity of cyanide see: cyanide poisoning .

Toxicity in humans

Human toxicity has not been well analyzed. Minimum threshold values for odor detections are reported to be at 7 ppm, with the majority of subjects detecting it at higher concentrations of 14 or 24 ppm. At concentrations of 24 ppm incidence of throat, eye and nose irritation occur. No deaths caused by methacrylonitrile poisoning have been reported. [12]

Effects on animals

Inhalation, and oral and dermal administration, of methacrylonitrile can cause acute deaths in animals, often preceded by convulsions and loss of consciousness. Signs of the toxic effects of methacrylonitrile in rats after oral absorption are ataxia, trembling, convulsions, mild diarrhea and irregular breathing. The main cause of toxic effects at lethal (and threshold) levels of MeAN is damage to the central nervous system. This, along with the signs of toxic effects displayed by all tested animals, is consistent with cyanide poisoning. Methacrylonitrile differs herein from acrylonitrile, which does not show cyanide related signs of toxicity.

Cyanide production after exposure to MeAN has been tested, and intravenous injection of MeAN in rabbits results in production of significant levels of cyanide in the blood. In Wistar rats too, toxicity is related to the in vivo liberation of cyanide after exposure to MeAN. The acute toxicity of MeAN can also be antagonized with cyanide antidotes.

A difference in resistance to the lethal effects of MeAN can be noted between species. For inhalation, a 4-hour exposure period gives a LC50 of 328-700 ppm for rats, 88 ppm for guinea pigs, 37 ppm for rabbits and 36 ppm for mice. In dogs acute lethality by inhalation is also noted, although no LC50 has been determined. Oral administration of MeAN has been tested on rats, mice and gerbils, showing a LD50 of 200 mg/kg for rats, 17 mg/kg for mice and 4 mg/kg for gerbils. Skin administration on rabbits causes death at a LC50 of 268 mg/kg. The NOAEL and LOAEL values for rats are determined at 50 mg/kg for NOAEL and 100 mg/kg for LOAEL. This is based on another sign of methacrylonitrile poisoning; urine retention, with 58% of rats showing bladder distention at an administered dose of 100 mg/kg.

Reproductive toxicity was tested in rats, but different outcomes have been reported. Willhite et al. suggest a LOAEL for reproductive effects of 50 mg/kg, while a report by the National Research Council claims no significant reproductive effects have been found.

Lastly, carcinogenic, mutagenic and genotoxic effects have been tested but unlike acrylonitrile, methacrylonitrile does not show signs of any such effects. [12] [5] [13]

Related Research Articles

Acrylonitrile is an organic compound with the formula CH2CHCN. It is a colorless volatile liquid although commercial samples can be yellow due to impurities. It has a pungent odor of garlic or onions. In terms of its molecular structure, it consists of a vinyl group linked to a nitrile. It is an important monomer for the manufacture of useful plastics such as polyacrylonitrile. It is reactive and toxic at low doses. Acrylonitrile was first synthesized by the French chemist Charles Moureu (1863–1929) in 1893.

Chlorfenvinphos Chemical compound

Chlorfenvinphos is the common name of an organophosphorus compound that was widely used as an insecticide and an acaricide. The molecule itself can be described as an enol ester derived from dichloroacetophenone and diethylphosphonic acid. Chlorfenvinphos has been included in many products since its first use in 1963. However, because of its toxic effect as a cholinesterase inhibitor it has been banned in several countries, including the United States and the European Union. Its use in the United States was cancelled in 1991.

<span class="mw-page-title-main">Ethion</span> Chemical compound

Ethion (C9H22O4P2S4) is an organophosphate insecticide. Ethion is known to affect a neural enzyme called acetylcholinesterase and prevent it from working.

Methylcholanthrene Chemical compound

Methylcholanthrene is a highly carcinogenic polycyclic aromatic hydrocarbon produced by burning organic compounds at very high temperatures. Methylcholanthrene is also known as 3-methylcholanthrene, 20-methylcholanthrene or the IUPAC name 3-methyl-1,2-dyhydrobenzo[j]aceanthrylene. The short notation often used is 3-MC or MCA. This compound forms pale yellow solid crystals when crystallized from benzene and ether. It has a melting point around 180 °C and its boiling point is around 280 °C at a pressure of 80 mmHg. Methylcholanthrene is used in laboratory studies of chemical carcinogenesis. It is an alkylated derivative of benz[a]anthracene and has a similar UV spectrum. The most common isomer is 3-methylcholanthrene, although the methyl group can occur in other places.

<span class="mw-page-title-main">Sudan I</span> Chemical compound

Sudan I, is an organic compound, typically classified as an azo dye. It is an intensely orange-red solid that is added to colourise waxes, oils, petrol, solvents, and polishes. Sudan I has also been adopted for colouring various foodstuffs, especially curry powder and chili powder, although the use of Sudan I in foods is now banned in many countries, because Sudan I, Sudan III, and Sudan IV have been classified as category 3 carcinogens by the International Agency for Research on Cancer. Sudan I is still used in some orange-coloured smoke formulations and as a colouring for cotton refuse used in chemistry experiments.

2-Butoxyethanol Chemical compound

2-Butoxyethanol is an organic compound with the chemical formula BuOC2H4OH (Bu = CH3CH2CH2CH2). This colorless liquid has a sweet, ether-like odor, as it derives from the family of glycol ethers, and is a butyl ether of ethylene glycol. As a relatively nonvolatile, inexpensive solvent, it is used in many domestic and industrial products because of its properties as a surfactant. It is a known respiratory irritant and can be acutely toxic, but animal studies did not find it to be mutagenic, and no studies suggest it is a human carcinogen. A study of 13 classroom air contaminants conducted in Portugal reported a statistically significant association with increased rates of nasal obstruction and a positive association below the level of statistical significance with a higher risk of obese asthma and increased child BMI.

4-Aminobiphenyl (4-APB) is an organic compound with the formula C6H5C6H4NH2. It is an amine derivative of biphenyl. It is a colorless solid, although aged samples can appear colored. 4-Aminobiphenyl was commonly used in the past as a rubber antioxidant and an intermediate for dyes. Exposure to this aryl-amine can happen through contact with chemical dyes and from inhalation of cigarette smoke. Researches showed that 4-aminobiphenyl is responsible for bladder cancer in humans and dogs by damaging DNA. Due to its carcinogenic effects, commercial production of 4-aminobiphenyl ceased in the United States in the 1950s.

Benzotrichloride Chemical compound

Benzotrichloride (BTC), also known as α,α,α-trichlorotoluene, phenyl chloroform or (trichloromethyl)benzene, is an organic compound with the formula C6H5CCl3. Benzotrichloride is an unstable, colorless (to yellowish), viscous, chlorinated hydrocarbon with a penetrating odor. Benzotrichloride is used extensively as a chemical intermediate for products of various classes, i.e. dyes and antimicrobial agents.

<i>o</i>-Toluidine Aryl amine

o-Toluidine (ortho-toluidine) is an organic compound with the chemical formula CH3C6H4NH2. It is the most important of the three isomeric toluidines. It is a colorless liquid although commercial samples are often yellowish. It is a precursor to the herbicides metolachlor and acetochlor.

1,1,2,2-Tetrachloroethane Chemical compound

1,1,2,2-tetrachloroethane (TeCA), also known as bonoform, cellon, or westron is a toxic, synthetic halogen rich alkane. It is colorless liquid and has a sweet odor. It is used as an industrial solvent or as a separation agent. TeCA can be inhaled, consumed or absorbed through the skin. After exposure, nausea, dizziness or even liver damage may occur.

Chlorethoxyfos Chemical compound

Chlorethoxyfos is an organophosphate acetylcholinesterase inhibitor used as an insecticide. It is registered for the control of corn rootworms, wireworms, cutworms, seed corn maggot, white grubs and symphylans on corn. The insecticide is sold under the trade name Fortress by E.I. du Pont de Nemours & Company.

Hexachlorocyclopentadiene Chemical compound

Hexachlorocyclopentadiene (HCCPD), also known as C-56, Graphlox, and HRS 1655, is an organochlorine compound with the formula C5Cl6. It is a precursor to pesticides, flame retardants, and dyes. It is a colourless liquid, although commercial samples appear lemon-yellow liquid sometimes with a bluish vapour. Many of its derivatives proved to be highly controversial, as studies showed them to be persistent organic pollutants. An estimated 270,000 tons were produced until 1976, and smaller amounts continue to be produced today. Two prominent manufacturers are Velsicol Chemical Corporation in the US and by Jiangsu Anpon Electrochemicals Co. in China.

Demeton Chemical compound

Demeton, sold as an amber oily liquid with a sulphur like odour under the name Systox™, is an organophosphate derivative causing irritability and shortness of breath to individuals repeatedly exposed. It was used as a phosphorothioate insecticide and acaricide and has the chemical formula C8H19O3PS2. Although it was previously used as an insecticide, it is now largely obsolete due to its relatively high toxicity to humans. Demeton consists of two components, demeton-S and demeton-O in a ratio of approximately 2:1 respectively. The chemical structure of demeton is closely related to military nerve agents such as VX and a derivative with one of the ethoxy groups replaced by methyl was investigated by both the US and Soviet chemical-weapons programs under the names V.sub.X and GD-7.

Carbophenothion Chemical compound

Carbophenothion also known as Stauffer R 1303 as for the manufacturer, Stauffer Chemical, is an organophosphorus chemical compound. It was used as a pesticide for citrus fruits under the name of Trithion. Carbophenothion was used as an insecticide and acaricide. Although not used anymore it is still a restricted use pesticide in the United States. The chemical is identified in the US as an extremely hazardous substance according to the Emergency Planning and Community Right-to-Know Act.

Sulfotep Chemical compound

Sulfotep (also known as tetraethyldithiopyrophosphate and TEDP) is a pesticide commonly used in greenhouses as a fumigant. The substance is also known as Dithione, Dithiophos, and many other names. Sulfotep has the molecular formula C8H20O5P2S2 and belongs to the organophosphate class of chemicals. It has a cholinergic effect, involving depression of the cholinesterase activity of the peripheral and central nervous system of insects. The transduction of signals is disturbed at the synapses that make use of acetylcholine. Sulfotep is a mobile oil that is pale yellow-colored and smells like garlic. It is primarily used as an insecticide.

Ethoprophos Chemical compound

Ethoprophos (or ethoprop) is an organophosphate ester with the formula C8H19O2PS2. It is a clear yellow to colourless liquid that has a characteristic mercaptan-like odour. It is used as an insecticide and nematicide and it is an acetylcholinesterase inhibitor.

Glycidamide Chemical compound

Glycidamide is an organic compound with the formula H2NC(O)C2H3O. It is a colorless, oil. Structurally, it contains adjacent amides and epoxide functional groups. It is a bioactive, potentially toxic or even carcinogenic metabolite of acrylonitrile and acrylamide. It is a chiral molecule.

<span class="mw-page-title-main">4-Ipomeanol</span> Chemical compound

4-Ipomeanol (4-IPO) is a pulmonary pre-toxin isolated from sweet potatoes infected with the fungus Fusarium solani. One of the 4-IPO metabolites is toxic to the lungs, liver and kidney in humans and animals. This metabolite can covalently bind to proteins, thereby interfering with normal cell processes.

Nivalenol Type of mycotoxin

Nivalenol (NIV) is a mycotoxin of the trichothecene group. In nature it is mainly found in fungi of the Fusarium species. The Fusarium species belongs to the most prevalent mycotoxin producing fungi in the temperate regions of the northern hemisphere, therefore making them a considerable risk for the food crop production industry.

PR toxin Chemical compound

Penicillin Roquefort Toxin is a mycotoxin produced by the fungi Penicillium roqueforti. In 1973, PR toxin was first partially characterized by isolating moldy corn on which the fungi had grown. Although its lethal dose was determined shortly after the isolation of the chemical, details of its toxic effects, were not fully clarified until 1982 in a study with mice, rats, anesthetized cats and preparations of isolated rat auricle.

References

  1. 1 2 3 4 5 6 NIOSH Pocket Guide to Chemical Hazards. "#0395". National Institute for Occupational Safety and Health (NIOSH).
  2. 1 2 3 Toxicology and Carcinogenesis Studies of Methacrylonitrile (CAS No. 126-98-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies)
  3. ↑ Methacrylonitrile, chemicalbook.com
  4. ↑ Baker, R.R., Dymond, H.F., and Skillabeer, P.K. (1984). Determination of "unsaturated compounds formed by a burning cigarette. Anal. Proc. 21, 135
  5. 1 2 3 4 5 6 Farooqui, M. Y. H. and M. M. Mumtaz (1991). "Toxicology of methacrylonitrile." Toxicology 65(3): 239-250.
  6. ↑ El Hadri, L., et al. (2005). "Comparative metabolism of methacrylonitrile and acrylonitrile to cyanide using cytochrome P4502E1 and microsomal epoxide hydrolase-null mice." Toxicology and Applied Pharmacology 205(2): 116-125.
  7. 1 2 Viel, P., et al. (1999). "Electropolymerization of methacrylonitrile on a rotating disk electrode at high spinning rate." Journal of Electroanalytical Chemistry 470(1): 14-22.
  8. ↑ Day, W. W., et al. (1988). "Interaction of methacrylonitrile with glutathione." Res Commun Chem Pathol Pharmacol 62(2): 267-278.
  9. ↑ Ghanayem et al., 1985 Committee on Acute Exposure Guideline Levels; Committee on Toxicology; Board on Environmental Studies and Toxicology; Division on Earth and Life Studies; National Research Council. Washington (DC): National Academies Press (US); 2014 Mar 21
  10. ↑ Abreu ME, Ahmed AE (1980) Metabolism of acrylonitrile to cyanide: In vitro studies. Drug Metab Dispos 8:376–379
  11. ↑ Ghanayem, B.I., Sanders, J.M., Chanas, B., Burka, L.T., and Gonzalez, F.J. (1999). Role of cytochrome P450 CYP2EI in methacrylonitrile metabolism and disposition. J. Pharmacol. Exp. Ther. 289, 1054-1059.
  12. 1 2 National Research Council. (2014). Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi:https://doi.org/10.17226/18707
  13. ↑ C.C. Willhite, V.H. Ferm and R.P. Smith, Teratogenic effect\ of aliphatic nitrilics Teratology. 23 (1981) 317.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.